1 Complete Record
99303478
Prognostic factors of oesophageal squamous cell carcinoma from the
perspective of
molecular biology.
Shimada Y; Imamura M; Watanabe G; Uchida S; Harada H; Makino T; Kano M
Department of Surgery and Surgical Basic Science, Graduate School of
Medicine,
Kyoto University, Japan.
British journal of cancer (SCOTLAND) Jun 1999 80 (8) p1281-8 ISSN:
0007-0920
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9909
Subfile: INDEX MEDICUS
Recent developments in molecular biology have revealed that several
oncogenes,
suppressor genes and adhesion molecules are involved in the development
of
oesophageal cancer; however, the role of these genes is still unknown.
To evaluate
which molecular biological factors are related to patients' prognosis
and recurrence,
we checked p53, p16, p21/Waf1, cyclin D1, Ki-67, epidermal growth factor
receptor
(EGFR), vascular endothelial growth factor (VEGF), Mdm2, Bcl2,
E-cadherin and MRP1/
CD9 by means of immunohistochemical analysis in 116 cases of oesophageal
cancer (R0).
We also checked the regrowth capability of the primary cultures of the
resected
tumours and the effect of post-operative treatment. Although univariate
analysis
revealed that pN (pTNM), pT (pTNM), sex, cyclin D1, Ki-67, VEGF,
E-cadherin and cell
regrowth capability were prognostic factors, multivariate analysis
revealed that pN
(risk ratio (RR) 3.17), sex (RR 8.13), cell regrowth capability (RR
3.03) and E-
cadherin (RR 0.30) were prognostic factors. Interestingly, step-wise
analysis
revealed that the following five factors were prognostic factors: pN (RR
5.74), sex
(RR 3.14), cyclin D1 (RR 2.29), E-cadherin (RR 0.26) and cell regrowth
capability (RR
1.94). Logistic regression analysis revealed that the risk factors of
haematogenous
recurrence were pN (odds ratio (OR) 8.97), cyclin D1 (OR 4.52) and EGFR
(OR 0.18).
On the other hand, the risk factor of lymph node recurrence was pN (OR
5.16). With
regard to the effect of postoperative treatment, post-operative
radiotherapy was a
favourable risk factor (RR 0.43) and reduced the haematogenous
recurrence (OR 0.18).
Our data indicate that combination analysis using pN, sex, cyclin D1,
E-cadherin,
EGFR and cell regrowth capability may be useful for the prediction of
patient
survival and recurrence.
Tags: Female; Human; Male; Support, Non-U.S. Gov't
Descriptors: *Carcinoma, Squamous Cell--Pathology--PA; *Esophageal
Neoplasms--
Pathology--PA; *Tumor Markers, Biological--Analysis--AN; Aged;
Cadherins--Analysis--
AN; Carcinoma, Squamous Cell--Genetics--GE; Carcinoma, Squamous
Cell--Radiotherapy--
RT; Cyclin D1--Analysis--AN; Esophageal Neoplasms--Genetics--GE;
Esophageal Neoplasms-
-Radiotherapy--RT; Immunohistochemistry; Middle Age; Neoplasm
Recurrence, Local;
Prognosis; Receptor, Epidermal Growth Factor--Analysis--AN; Risk
Factors; Survival
Analysis; Treatment Outcome
CAS Registry No.: 0 (Cadherins); 0 (Tumor Markers, Biological);
136601-57-5
(Cyclin D1)
Enzyme No.: EC 2.7.11.- (Receptor, Epidermal Growth Factor)
13 Complete Record
99334886
Bcl10 is not a target for frequent mutation in human carcinomas.
Lambers AR; Gumbs C; Ali S; Marks JR; Iglehart JD; Berchuck A; Futreal
PA
Department of Surgery, Duke University Medical Center, Durham, NC
27710, USA.
British journal of cancer (SCOTLAND) Jul 1999 80 (10) p1575-6
ISSN: 0007-0920
Contract/Grant No.: P50-CA68438--CA--NCI
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9909
Subfile: INDEX MEDICUS
The recently described Bcl10 gene has been suggested to be a major
target gene for
inactivation in a variety of human cancers. In order to further
evaluate the role of
this gene in human adult malignancies, we have analysed a series of
carcinomas for
mutations in the Bcl10 gene. We have screened a panel of 174 carcinoma
samples in
total, comprised of 47 breast, 36 epithelial ovarian, 36 endometrial, 12
cervical, 23
colorectal and 20 head/neck carcinomas, all unselected for grade or
stage. This
panel reflects, in part, tumours reported to have involvement of the
1p22 region of
chromosome 1, the region harbouring the Bcl10 gene. No deleterious
mutations were
detected in any of the samples analysed, strongly suggesting that Bcl10
is not a
common target for inactivation in adult malignancies and that BCL10 is
not the gene
targeted for frequent inactivation at 1p22.
Tags: Female; Human; Support, Non-U.S. Gov't; Support, U.S. Gov't,
P.H.S.
Descriptors: *Colorectal Neoplasms--Genetics--GE; *Genital Neoplasms,
Female--
Genetics--GE; *Head and Neck Neoplasms--Genetics--GE; *Mutation;
*Neoplasm Proteins--
Genetics--GE; Adult; Polymerase Chain Reaction; Polymorphism,
Single-Stranded
Conformational
CAS Registry No.: 0 (Bcl10 protein); 0 (Neoplasm Proteins)
14 Complete Record
99334885
Lack of Bcl10 mutations in testicular germ cell tumours and derived
cell lines.
van Schothorst EM; Mohkamsing S; van Gurp RJ; Oosterhuis JW; van der
Saag PT;
Looijenga LH
Laboratory for Experimental Patho-Oncology, Pathology/Daniel den Hoed
Cancer
Center, Josephine Nefkens Institute, University Hospital Rotterdam, The
Netherlands.
British journal of cancer (SCOTLAND) Jul 1999 80 (10) p1571-4
ISSN: 0007-0920
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9909
Subfile: INDEX MEDICUS
Aberrations within Bcl10, a gene involved in execution of apoptosis,
has most
recently been found in a variety of cancers, including cell lines of
testicular germ
cell tumours of adolescents and adults (TGCTs). To study this in more
detail, we
screened exons 2 and 3 of this gene for mutations in a larger series of
cell lines as
well as primary TGCTs by single-strand conformation polymorphism and
endonuclease
restriction analysis. Because no aberrations were detected, we conclude
that
inactivation of Bcl10 by mutation is at least far less important in the
development
of TGCTs than proposed.
Tags: Human; Male; Support, Non-U.S. Gov't
Descriptors: *Germinoma--Genetics--GE; *Neoplasm
Proteins--Genetics--GE;
*Testicular Neoplasms--Genetics--GE; Adolescence; Adult; Base Sequence;
DNA, Neoplasm;
Exons; Germinoma--Pathology--PA; Molecular Sequence Data; Polymorphism,
Single-
Stranded Conformational; Testicular Neoplasms--Pathology--PA; Tumor
Cells, Cultured
CAS Registry No.: 0 (Bcl10 protein); 0 (DNA, Neoplasm); 0
(Neoplasm Proteins)
15 Complete Record
99334884
Mutations in Bcl10 are very rare in colorectal cancer.
Stone JG; Rowan AJ; Tomlinson IP; Houlston RS
Section of Cancer Genetics, Institute of Cancer Research, Sutton,
Surrey, UK.
British journal of cancer (SCOTLAND) Jul 1999 80 (10) p1569-70
ISSN: 0007-0920
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9909
Subfile: INDEX MEDICUS
Bcl10 is a recently identified gene reported to be involved commonly
in human
malignancy (Willis et al (1999) Cell 96: 1-20). To investigate whether
it is
frequently mutated in colorectal cancer we have analysed a series of 132
colorectal
cancers and eight colorectal cancer cell lines for mutations in Bcl10.
One feature
of the Bcl10 gene is that it harbours two polyadenine tracts. These
repeating
elements in genes can be prone to a high rate of mutation if there is
defective
mismatch repair. To examine the possibility that Bcl10 may be
preferentially mutated
in mismatch repair-deficient cancers, 49 of the tumours and cell lines
were known to
be replication error (RER)-positive and, of these, ten were from
individuals
harbouring germline mutations in hMLH1 or hMSH2. No pathogenic
mutations were
detected in the tumours and only one mutation was found in the
colorectal cancer cell
lines. These results indicate that Bcl10 is unlikely to be involved in
the pathways
of colorectal carcinogenesis.
Tags: Human; Support, Non-U.S. Gov't
Descriptors: *Colorectal Neoplasms--Genetics--GE; *Mutation; *Neoplasm
Proteins--
Genetics--GE; Polymerase Chain Reaction; Polymorphism, Single-Stranded
Conformational;
Tumor Cells, Cultured
CAS Registry No.: 0 (Bcl10 protein); 0 (Neoplasm Proteins)
16 Complete Record
99334883
BCL10 is rarely mutated in human prostate carcinoma, small-cell lung
cancer, head
and neck tumours, renal carcinoma and sarcomas. MPT Collaborators, St
George's
Hospital Collaborators.
Gill S; Broni J; Jefferies S; Osin P; Kovacs G; Maitland NJ; Eeles R;
Edwards SM;
Dyer MJ; Willis TG; Cooper CS
Section of Molecular Carcinogenesis, Institute of Cancer Research,
Sutton, Surrey,
UK.
British journal of cancer (SCOTLAND) Jul 1999 80 (10) p1565-8
ISSN: 0007-0920
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9909
Subfile: INDEX MEDICUS
We have used single-strand conformation polymorphism (SSCP) analysis
to screen for
mutations in the BCL10 gene in 81 primary prostate carcinomas, 20
squamous cell
cancers of the head and neck, 15 small-cell lung cancer cell lines, 24
renal
carcinoma cell lines and 13 sarcoma cell lines. We failed to find
evidence of
somatically acquired mutations of the BCL10 gene suggesting that BCL10
does not play
a major role in the development of these malignancies.
Tags: Human; Male; Support, Non-U.S. Gov't
Descriptors: *Head and Neck Neoplasms--Genetics--GE; *Kidney
Neoplasms--Genetics--
GE; *Mutation; *Neoplasm Proteins--Genetics--GE; *Prostatic
Neoplasms--Genetics--GE;
Head and Neck Neoplasms--Pathology--PA; Kidney Neoplasms--Pathology--PA;
Polymerase
Chain Reaction; Polymorphism, Single-Stranded Conformational; Prostatic
Neoplasms--
Pathology--PA
CAS Registry No.: 0 (Bcl10 protein); 0 (Neoplasm Proteins)
19 Complete Record
99303796
Distinct glucocorticoid receptor transcriptional regulatory surfaces
mediate the
cytotoxic and cytostatic effects of glucocorticoids.
Rogatsky I; Hittelman AB; Pearce D; Garabedian MJ
Department of Microbiology and the Kaplan Comprehensive Cancer Center,
New York
University School of Medicine, New York, New York 10016, USA.
Molecular and cellular biology (UNITED STATES) Jul 1999 19 (7)
p5036-49 ISSN:
0270-7306 Contract/Grant No.: 5T32AI07180-17--AI--NIAID;
2T32GM07308--GM--NIGMS; R29-
DK51151-03--DK--NIDDK
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9909
Subfile: INDEX MEDICUS
Glucocorticoids act through the glucocorticoid receptor (GR), which
can function as
a transcriptional activator or repressor, to elicit cytostatic and
cytotoxic effects
in a variety of cells. The molecular mechanisms regulating these events
and the
target genes affected by the activated receptor remain largely
undefined. Using
cultured human osteosarcoma cells as a model for the GR
antiproliferative effect, we
demonstrate that in U20S cells, GR activation leads to irreversible
growth
inhibition, apoptosis, and repression of Bcl2. This cytotoxic effect is
mediated by
GR's transcriptional repression function, since
transactivation-deficient mutants and
ligands still bring about apoptosis and Bcl2 down-regulation. In
contrast, the
antiproliferative effect of GR in SAOS2 cells is reversible, does not
result in
apoptosis or repression of Bcl2, and is a function of the receptor's
ability to
stimulate transcription. Thus, the cytotoxic versus cytostatic outcome
of
glucocorticoid treatment is cell context dependent. Interestingly, the
cytostatic
effect of glucocorticoids in SAOS2 cells involves multiple GR activation
surfaces.
GR mutants and ligands that disrupt individual transcriptional
activation functions
(activation function 1 {AF-1} and AF-2) or receptor dimerization fail to
fully
inhibit cellular proliferation and, remarkably, discriminate between the
targets of
GR's cytostatic action, the cyclin-dependent kinase inhibitors p21(Cip1)
and
p27(Kip1). Induction of p21(Cip1) is agonist dependent and requires
AF-2 but not AF-
1 or GR dimerization. In contrast, induction of p27(Kip1) is agonist
independent,
does not require AF-2 or AF-1, but depends on GR dimerization. Our
findings indicate
that multiple GR transcriptional regulatory mechanisms that employ
distinct receptor
surfaces are used to evoke either the cytostatic or cytotoxic response
to
glucocorticoids.
Tags: Human; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't,
P.H.S.
Descriptors: *Antineoplastic Agents--Metabolism--ME; *Apoptosis;
*Glucocorticoids--
Metabolism--ME; *Receptors, Glucocorticoid--Metabolism--ME; Cell Cycle;
Cyclins--
Metabolism--ME; Cytotoxicity, Immunologic; Dimerization;
Microtubule-Associated
Proteins--Metabolism--ME; Mifepristone--Pharmacology--PD; Mutagenesis;
Proto-Oncogene
Proteins c-bcl-2--Biosynthesis--BI; Receptors,
Glucocorticoid--Agonists--AG;
Receptors, Glucocorticoid--Genetics--GE; Trans-Activation (Genetics);
Tumor Cells,
Cultured
CAS Registry No.: 0 (Antineoplastic Agents); 0 (Cip1 protein); 0
(Cyclins); 0
(Glucocorticoids); 0 (Microtubule-Associated Proteins); 0
(Proto-Oncogene
Proteins c-bcl-2); 0 (Receptors, Glucocorticoid); 147604-94-2 (KIP1
protein);
84371-65-3 (Mifepristone)
20 Complete Record
99281267
Expression of MPM2, p53 and Bcl2 proteins in Hodgkin's disease.
DziecioL J; MaLdyk J; Zimnoch L; Szczepanski M
Department of Pathological Anatomy, Medical School, BiaLystok, Poland.
Folia histochemica et cytobiologica (POLAND) 1999 37 (2) p147-8
ISSN: 0239-8508
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9909
Subfile: INDEX MEDICUS
Tags: Comparative Study; Human
Descriptors: *Hodgkin Disease--Metabolism--ME;
*Phosphoproteins--Analysis--AN;
*Protein p53--Analysis--AN; *Proto-Oncogene Proteins
c-bcl-2--Analysis--AN;
Adolescence; Adult; Cell Nucleus--Chemistry--CH; Cell
Nucleus--Pathology--PA; Child;
Hodgkin Disease--Pathology--PA; Immunohistochemistry; Middle Age;
Phosphoproteins--
Biosynthesis--BI; Prognosis; Protein p53--Biosynthesis--BI;
Proto-Oncogene Proteins c-
bcl-2--Biosynthesis--BI; Retrospective Studies
CAS Registry No.: 0 (MPM2-reactive phosphoprotein 1); 0
(Phosphoproteins); 0
(Protein p53); 0 (Proto-Oncogene Proteins c-bcl-2)
21 Complete Record
99308628
Absence of BCL10 mutations in human malignant mesothelioma {comment}
Apostolou S; De Rienzo A; Murthy SS; Jhanwar SC; Testa JR
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Cell (UNITED STATES) Jun 11 1999 97 (6) p684-6; discussion 686-8
ISSN: 0092-
8674
Note: Comment on: Cell 1999 Jan 8;96(1):35-45
Language: ENGLISH
Document Type: COMMENT; JOURNAL ARTICLE
Journal Announcement: 9909
Subfile: INDEX MEDICUS
Tags: Human
Descriptors: *Mesothelioma--Genetics--GE; *Mutation; *Neoplasm
Proteins--Genetics--
GE; DNA, Neoplasm--Analysis--AN; Genes, Suppressor, Tumor; Loss of
Heterozygosity;
Polymorphism, Single-Stranded Conformational; Tumor Cells, Cultured
CAS Registry No.: 0 (Bcl10 protein); 0 (DNA, Neoplasm); 0
(Neoplasm Proteins)
22 Complete Record
99308627
Lack of BCL10 mutations in germ cell tumors and B cell lymphomas
{comment}
Fakruddin JM; Chaganti RS; Murty VV
Department of Pathology, College of Physicians and Surgeons, Columbia
University,
New York, New York 10032, USA.
Cell (UNITED STATES) Jun 11 1999 97 (6) p683-4; discussion 686-8
ISSN: 0092-
8674
Note: Comment on: Cell 1999 Jan;96(1):35-45
Language: ENGLISH
Document Type: COMMENT; JOURNAL ARTICLE
Journal Announcement: 9909
Subfile: INDEX MEDICUS
Tags: Human; Male
Descriptors: *Germinoma--Genetics--GE; *Lymphoma,
B-Cell--Genetics--GE; *Mutation;
*Neoplasm Proteins--Genetics--GE; Polymorphism, Single-Stranded
Conformational
CAS Registry No.: 0 (Bcl10 protein); 0 (Neoplasm Proteins)
24 Complete Record
99277834
BCL2 overexpression in diffuse large B-cell lymphoma.
Monni O; Franssila K; Joensuu H; Knuutila S
Department of Medical Genetics, Haartman Institute and Helsinki
University Central
Hospital, University of Helsinki, Finland.
Leukemia & lymphoma (SWITZERLAND) Jun 1999 34 (1-2) p45-52 ISSN:
1042-8194
Language: ENGLISH
Document Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
Journal Announcement: 9909
Subfile: INDEX MEDICUS
Translocation (14;18)(q32;q21), which is detected in 20-30% of diffuse
large B-cell
lymphomas (DLBCL), is regarded as a major mechanism for BCL2 protein
overexpression.
Nevertheless, BCL2 overexpression is not always caused by t(14;18),
because it is
often detected in lymphomas without BCL2 rearrangement. Recent studies
have shown
that increased expression of BCL2 may also result from BCL2 gene
amplification in
DLBCL. Similarly, it has been speculated that the mutations of the open
reading
frame might cause increased expression of BCL2 by affecting the
interactions of BCL2
with other proteins. The results obtained from studies on the
association of BCL2
protein overexpression with survival of DLBCL are controversial,
although a
correlation with decreased overall survival seems to exist. However,
BCL2
rearrangement does not seem to have any major association with poor
prognosis, but it
is difficult to assess its true impact on prognosis due to differences
in treatment
and follow-up, and methodologies applied to study the BCL2
rearrangement. This
review summarizes the BCL2 expression studies in DLBCL and discusses the
prognostic
relevance of BCL2 overexpression and its mechanisms. (60 References)
Tags: Animal; Human
Descriptors: *Lymphoma, B-Cell--Metabolism--ME; *Lymphoma, Large-Cell,
Diffuse--
Metabolism--ME; *Proto-Oncogene Proteins c-bcl-2--Biosynthesis--BI;
Lymphoma, B-Cell--
Genetics--GE; Lymphoma, Large-Cell, Diffuse--Genetics--GE;
Proto-Oncogene Proteins c-
bcl-2--Genetics--GE
CAS Registry No.: 0 (Proto-Oncogene Proteins c-bcl-2)
30 Complete Record
99250774
Linkage analysis of multiple sclerosis with candidate region markers
in Sardinian
and Continental Italian families.
D'Alfonso S; Nistico L; Zavattari P; Marrosu MG; Murru R; Lai M;
Massacesi L;
Ballerini C; Gestri D; Salvetti M; Ristori G; Bomprezzi R; Trojano M;
Liguori M;
Gambi D; Quattrone A; Fruci D; Cucca F; Richiardi PM; Tosi R
Chair of Human Genetics, University of Piemonte Orientale A. Avogadro,
Novara,
Italy.
European journal of human genetics (ENGLAND) Apr 1999 7 (3) p377-85
ISSN: 1018-
4813
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9909
Subfile: INDEX MEDICUS
Previous genome screens in multiple sclerosis have shown some evidence
of linkage
in scattered chromosomal regions. Although in no case the evidence of
each single
study was compelling and although in general the linkage 'peaks' of the
different
studies did not coincide, some regions can be considered likely
candidates for the
presence of MS risk genes because of the clustering of MLS scores and
homology with
eae loci. We performed a linkage analysis of markers in these regions
and of
intragenic markers of some individual candidate genes (HLA-DRB1, CTLA-4,
IL9, APOE,
BCL2, TNFR2). For the first time, Southern European populations were
targeted,
namely Continental Italians and Sardinians. A total of 69 multiplex
families were
typed for 67 markers by a semi-automatic fluorescence-based assay.
Results were
analysed for linkage by two non-parametric tests: GENEHUNTER and SimIBD.
In general,
the linkage scores obtained were low, confirming the conclusion that no
gene is
playing a major role in the disease. However, some markers, in 2p11,
3q21.1, 7p15.2
and 22q13.1 stood out as promising since they showed higher scores with
one or the
other test. This stimulates further association analysis of a large
number of
simplex families from the same populations.
Tags: Human; Support, Non-U.S. Gov't
Descriptors: *Linkage (Genetics); *Multiple Sclerosis--Genetics--GE;
Genetic
Markers; Italy
CAS Registry No.: 0 (Genetic Markers)
31 Complete Record
99290792
Increased number of chromosomal imbalances and high-level DNA
amplifications in
mantle cell lymphoma are associated with blastoid variants.
Bea S; Ribas M; Hernandez JM; Bosch F; Pinyol M; Hernandez L; Garcia
JL; Flores T;
Gonzalez M; Lopez-Guillermo A; Piris MA; Cardesa A; Montserrat E; Miro
R; Campo E
Hematopathology Section, Laboratory of Anatomic Pathology, Department
of
Hematology, Hospital Clinic, Villarroel, 170, 08036-Barcelona, Spain.
Blood (UNITED STATES) Jun 15 1999 93 (12) p4365-74 ISSN: 0006-4971
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9909
Subfile: AIM; INDEX MEDICUS
Mantle cell lymphomas (MCLs) are characterized by 11q13 chromosomal
translocations
and cyclin D1 overexpression. The secondary genetic and molecular
events involved in
the progression of these tumors are not well known. In this study, we
have analyzed
45 MCLs (32 typical and 13 blastoid variants) by comparative genomic
hybridization
(CGH). To identify the possible genes included in the abnormal
chromosome regions,
selected cases were analyzed for P53, P16(INK4a), RB, C-MYC, N-MYC,
BCL2, BCL6, CDK4,
and BMI-1 gene alterations. The most frequent imbalances detected by
CGH were gains
of chromosomes 3q (49%), 7p (27%), 8q (22%), 12q (20%), 18q (18%), and
9q34 (16%) and
losses of chromosomes 13 (44%), 6q (27%), 1p (24%), 11q14-q23 (22%),
10p14-p15 (18%),
17p (16%), and 9p (16%). High-level DNA amplifications were identified
in 11
different regions of the genome, predominantly in 3q27-q29 (13%), 18q23
(9%), and
Xq28 (7%). The CGH analysis allowed the identification of regional
consensus areas
in most of the frequently involved chromosomes. Chromosome gains (P =.
02) and
losses (P =.01) and DNA amplifications (P =.015) were significantly
higher in
blastoid variants. The significant differences between blastoid and
typical tumors
were gains of 3q, 7p, and 12q, and losses of 17p. CGH losses of 17p
correlated with
P53 gene deletions and mutations. Similarly, gains of 12q and
high-level DNA
amplifications of 10p12-p13 were associated with CDK4 and BMI-1 gene
amplifications,
respectively. One of 2 cases with 8q24 amplification showed C-MYC
amplification by
Southern blot. Alterations in 2p, 3q, 13, and 18q were not associated
with N-MYC,
BCL6, RB, or BCL2 alterations, respectively, suggesting that other genes
may be the
targets of these genetic abnormalities in MCLs. Increased number of
gains (0 v 1-4 v
>4 gains per case) (P =.002), gains of 3q (P =.02), gains of 12q (P
=.03), and losses
of 9p (P =. 003) were significantly associated with a shorter survival
of the
patients. These results indicate that an increased number of chromosome
imbalances
are associated with blastoid variants of MCLs and may have prognostic
significance.
Tags: Female; Human; Male; Support, Non-U.S. Gov't
Descriptors: *Chromosome Aberrations; *Gene Amplification;
*Lymphocytes--Pathology--
PA; *Lymphoma, Small Cleaved-Cell, Diffuse--Genetics--GE; *Lymphoma,
Small Cleaved-
Cell, Diffuse--Pathology--PA; Blotting, Southern; Chromosome Deletion;
Chromosomes,
Human, Pair 12; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 3;
Chromosomes,
Human, Pair 7; Nucleic Acid Hybridization; Translocation (Genetics)
37 Complete Record
99257285
Aggressive mucosa associated lymphoid tissue lymphomas are associated
with
mutations in Bcl10.
Spencer J
Department of Histopathology, Guy's, King's and St Thomas' Medical
School, St
Thomas' Campus, Lambeth palace Road, London SE1 7EH, UK
j.spencer@umds.ac.uk
Gut (ENGLAND) Jun 1999 44 (6) p778-9 ISSN: 0017-5749
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9908
Subfile: AIM; INDEX MEDICUS
Tags: Human
Descriptors: *Frameshift Mutation; *Lymphoma, Mucosa-Associated
Lymphoid Tissue--
Genetics--GE; *Neoplasm Proteins--Genetics--GE; Apoptosis--Genetics--GE;
Chromosome
Abnormalities; Chromosomes, Human, Pair 1; NF-kappa B--Metabolism--ME;
Tumor Cells,
Cultured
CAS Registry No.: 0 (Bcl10 protein); 0 (Neoplasm Proteins); 0
(NF-kappa B)
38 Complete Record
99276903
Four cases of follicular lymphoma with t(14;18)(q32;q21) and
t(3;4)(q27;p13) with
LAZ3 (BCL6) rearrangement.
Daudignon A; Bisiau H; Le Baron F; Lai JL; Wetterwald M;
Galiegue-Zouitina S; Morel
P; Duthilleul P
Departement d'Hematologie-Immunologie-Cytogenetique, Centre
Hospitalier de
Valenciennes, France.
Cancer genetics and cytogenetics (UNITED STATES) Jun 1999 111 (2)
p157-60
ISSN: 0165-4608
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9908
Subfile: INDEX MEDICUS
We report four cases of follicular lymphoma with both
t(14;18)(q32;q21) and the
newly characterized t(3;4)(q27;p13). Molecular investigation confirmed
LAZ3 (BCL6)
rearrangement for all patients. The 3q27 aberrations have been rarely
described in
low-grade lymphomas and may represent secondary events whose implication
remains to
be elucidated.
Tags: Case Report; Female; Human
Descriptors: *Chromosomes, Human; *DNA-Binding Proteins--Genetics--GE;
*Lymphoma,
Follicular--Genetics--GE; *Proto-Oncogene Proteins--Genetics--GE;
*Transcription
Factors--Genetics--GE; *Translocation (Genetics); Adult; Aged; Blotting,
Southern;
Chromosomes, Human, Pair 14; Chromosomes, Human, Pair 18; Chromosomes,
Human, Pair 3;
Chromosomes, Human, Pair 4; Gene Rearrangement, B-Lymphocyte;
Karyotyping; Lymphoma,
Follicular--Drug Therapy--DT; Lymphoma, Non-Hodgkin; Middle Age; Zinc
Fingers--
Genetics--GE
CAS Registry No.: 0 (proto-oncogene protein bcl-6); 0 (DNA-Binding
Proteins); 0
(Proto-Oncogene Proteins); 0 (Transcription Factors)
39 Complete Record
99107122
Genetic characterization of HHV-8/KSHV-positive primary effusion
lymphoma reveals
frequent mutations of BCL6: implications for disease pathogenesis and
histogenesis.
Gaidano G; Capello D; Cilia AM; Gloghini A; Perin T; Quattrone S;
Migliazza A; Lo
Coco F; Saglio G; Ascoli V; Carbone A
Department of Medical Sciences, University of Torino at Novara, Italy.
giadano@med.no.unipmn.it
Genes, chromosomes & cancer (UNITED STATES) Jan 1999 24 (1) p16-23
ISSN: 1045-
2257
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9908
Subfile: INDEX MEDICUS
Human herpesvirus-8/Kaposi sarcoma-associated herpesvirus-positive
primary effusion
lymphoma (PEL) is a recently identified B-cell non-Hodgkin lymphoma
category
characterized by liquid growth in the serous body cavities. Apart from
viral
infection, no genetic alteration is known to be associated with PEL and
no recurrent
cytogenetic abnormality has been identified in these lymphomas. Yet the
consistent
monoclonality of PEL indicates that the disease is not solely a
virus-driven
proliferation. Here we report that PEL is associated with a high
frequency of
mutations of BCL6 5' noncoding regions, and we identify karyotypic
abnormalities that
may be recurrently involved in these lymphomas. Mutations of BCL-6 5'
noncoding
regions occurred in 8/13 PEL. Mutations occurred in the absence of BCL6
gross
rearrangements were often multiple in the same patient (7/8 mutated
cases), and
occurred in both HIV-positive and HIV-negative individuals. Since BCL6
mutations are
regarded as a genetic marker of B-cell transition through the germinal
center (GC),
these data are consistent with histogenetic derivation of PEL from GC or
post-GC B-
cells. Cytogenetic and FISH analysis of seven PEL cell lines showed
frequent
occurrence of complete or partial trisomy 12 (7/7 cases), trisomy 7 (4/7
cases), and
abnormalities of bands Iq21-25 (5/7 cases).
Tags: Human; Support, Non-U.S. Gov't
Descriptors: *DNA-Binding Proteins--Genetics--GE; *Genetic
Predisposition to
Disease--Genetics--GE; *Herpesviridae Infections--Etiology--ET;
*Herpesvirus, Kaposi
Sarcoma-Associated--Pathogenicity--PY; *Lymphoma--Etiology--ET;
*Mutation--Genetics--
GE; *Proto-Oncogene Proteins--Genetics--GE; *Transcription
Factors--Genetics--GE; DNA
Mutational Analysis; Herpesviridae Infections--Pathology--PA; In Situ
Hybridization,
Fluorescence; Karyotyping; Lymphoma--Genetics--GE;
Lymphoma--Pathology--PA; Tumor
Cells, Cultured; 5' Untranslated Regions--Genetics--GE
CAS Registry No.: 0 (proto-oncogene protein bcl-6); 0 (DNA-Binding
Proteins); 0
(Proto-Oncogene Proteins); 0 (Transcription Factors); 0 (5'
Untranslated
Regions)
42 Complete Record
99250533
Analysis of internal deletions within the BCL6 gene in B-cell
non-Hodgkin's
lymphoma.
Nakamura Y; Saito K; Furusawa S
Third Department of Internal Medicine, Dokkyo University School of
Medicine,
Tochigi, Japan.
British journal of haematology (ENGLAND) Apr 1999 105 (1) p274-7
ISSN: 0007-
1048
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9908
Subfile: INDEX MEDICUS
The BCL6 gene is frequently altered by chromosomal translocations
and/or point
mutations at its 5' non-coding portion in B-cell non-Hodgkin's lymphoma
(B-NHL). We
analysed submicroscopic structural alterations of the BCL6 gene which
had arisen from
internal deletion in four cases with B-NHL and found that these
deletions overlapped
at the 280 bp region in the first intron. In electrophoretic mobility
shift assay,
nuclear extracts prepared from various cell lines were shown to bind to
a fragment
from this commonly deleted region. Our results suggest that
deregulation of BCL6
expression would be caused by loss of this putative protein-binding
sequence in some
B-NHL cases.
Tags: Human; Support, Non-U.S. Gov't
Descriptors: *DNA-Binding Proteins--Genetics--GE; *Lymphoma,
B-Cell--Genetics--GE;
*Proto-Oncogene Proteins--Genetics--GE; *Transcription
Factors--Genetics--GE; Base
Sequence; Gene Deletion; Molecular Sequence Data
CAS Registry No.: 0 (proto-oncogene protein bcl-6); 0 (DNA-Binding
Proteins); 0
(Proto-Oncogene Proteins); 0 (Transcription Factors)
46 Complete Record
99251581
Inactivating mutations and overexpression of BCL10, a caspase
recruitment domain-
containing gene, in MALT lymphoma with t(1;14)(p22;q32).
Zhang Q; Siebert R; Yan M; Hinzmann B; Cui X; Xue L; Rakestraw KM;
Naeve CW;
Beckmann G; Weisenburger DD; Sanger WG; Nowotny H; Vesely M;
Callet-Bauchu E; Salles
G; Dixit VM; Rosenthal A; Schlegelberger B; Morris SW
Department of Pathology and Laboratory Medicine, St. Jude Children's
Research
Hospital, Memphis, Tennessee 38105, USA.
Nature genetics (UNITED STATES) May 1999 22 (1) p63-8 ISSN:
1061-4036
Contract/Grant No.: CA-27165--CA--NCI
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9907
Subfile: INDEX MEDICUS
Mucosa-associated lymphoid tissue (MALT) lymphomas most frequently
involve the
gastrointestinal tract and are the most common subset of extranodal
non-Hodgkin
lymphoma (NHL). Here we describe overexpression of BCL10, a novel
apoptotic
signalling gene that encodes an amino-terminal caspase recruitment
domain (CARD), in
MALT lymphomas due to the recurrent t(1;14)(p22;q32). BCL10 cDNAs from
t(1;14)-
positive MALT tumours contained a variety of mutations, most resulting
in truncations
either in or carboxy terminal to the CARD. Wild-type BCL10 activated
NF-kappaB but
induced apoptosis of MCF7 and 293 cells. CARD-truncation mutants were
unable to
induce cell death or activate NF-kappaB, whereas mutants with C-terminal
truncations
retained NF-kappaB activation but did not induce apoptosis. Mutant
BCL10
overexpression might have a twofold lymphomagenic effect: loss of BCL10
pro-apoptosis
may confer a survival advantage to MALT B-cells, and constitutive
NF-kappaB
activation may provide both anti-apoptotic and proliferative signals
mediated via its
transcriptional targets.
Tags: Female; Human; Male; Support, Non-U.S. Gov't; Support, U.S.
Gov't, P.H.S.
Descriptors: *Caspases--Metabolism--ME; *Lymphoma, Mucosa-Associated
Lymphoid
Tissue--Genetics--GE; *Neoplasm Proteins--Genetics--GE; Amino Acid
Sequence; Binding
Sites; Blotting, Northern; Cell Death--Genetics--GE; Cell Line;
Chromosomes, Human,
Pair 1--Genetics--GE; Chromosomes, Human, Pair 14--Genetics--GE;
DNA--Chemistry--CH;
DNA--Genetics--GE; Gene Expression Regulation, Neoplastic; In Situ
Hybridization,
Fluorescence; Molecular Sequence Data; Mutation; Neoplasm
Proteins--Chemistry--CH;
Neoplasm Proteins--Metabolism--ME; NF-kappa B--Metabolism--ME; Protein
Structure,
Tertiary; Sequence Alignment; Sequence Analysis, DNA; Sequence Homology,
Amino Acid;
Tissue Distribution; Translocation (Genetics); Tumor Cells, Cultured
Molecular Sequence Databank No.: GENBANK/AF097732; GENBANK/AF082283;
GENBANK/
AA654174; GENBANK/AA731881; GENBANK/AA761849; GENBANK/AA767451
CAS Registry No.: 0 (Bcl10 protein); 0 (Neoplasm Proteins); 0
(NF-kappa B);
9007-49-2 (DNA)
Enzyme No.: EC 3.4.22.- (Caspases)
47 Complete Record
99039812
Deregulation of BCL6 in non-Hodgkin lymphoma by insertion of IGH
sequences in
complex translocations involving band 3q27.
Chaganti SR; Rao PH; Chen W; Dyomin V; Jhanwar SC; Parsa NZ;
Dalla-Favera R;
Chaganti RS
Laboratory of Cancer Genetics, Sloan-Kettering Institute for Cancer
Research,
Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Genes, chromosomes & cancer (UNITED STATES) Dec 1998 23 (4) p328-36
ISSN: 1045-
2257 Contract/Grant No.: CA66699--CA--NCI; CA44029--CA--NCI
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9907
Subfile: INDEX MEDICUS
Chromosomal band 3q27 frequently engages in translocations with a
number of sites
within the genome, including those containing IG and other genes, during
the
development of B-cell lymphoma. The BCL6 gene, mapped at 3q27, is
deregulated in
these translocations and was isolated from a t(3;14)(q27;q32)
translocation. It
encodes a zinc-finger transcription repressor protein, which is
expressed mainly in
the germinal center (GC) B cells and plays a key role in GC development
and T-cell-
dependent immune response. BCL6 deregulation in 3q27 translocations is
brought about
by substitution of its 5' regulatory sequences by promoters of the
rearranging genes.
BCL6-rearranging genes studied so far (IGH, IGLL, TTF, BOBI, H4)
displayed a broader
pattern of expression than BCL6 during B-cell development. This
observation has led
to the suggestion that continued expression of BCL6 beyond its
developmentally
regulated point of downregulation under the direction of substituted
promoters may
keep the GC B cell in a cycling mode and lead to clonal expansion and
lymphoma
development. However, the rearranging partners of BCL6 in several of
the 3q27
translocations have not yet been identified. In a molecular cloning
analysis of two
such translocations, t(1;3)(q21;q27) and t(3;6)(q27;p25), and an
immunoblastic
lymphoma cell line, OSI-LY8, we identified a novel mechanism of BCL6
deregulation.
This comprised replacement of BCL6 5' regulatory sequences by insertion
of IG gene
transcriptional regulatory sequences at the translocation junction.
These studies
demonstrate novel features of instability of 3q27, and of the BCL6 and
IGH genes, in
B-cell lymphomagenesis.
Tags: Female; Human; Male; Support, U.S. Gov't, P.H.S.
Descriptors: *DNA-Binding Proteins--Genetics--GE;
*Immunoglobulins--Genetics--GE;
*Lymphoma, Mixed-Cell, Diffuse--Genetics--GE; *Lymphoma,
Non-Hodgkin--Genetics--GE;
*Proto-Oncogene Proteins--Genetics--GE; *Transcription
Factors--Genetics--GE;
*Translocation (Genetics)--Genetics--GE; Base Sequence; Chromosome
Mapping;
Chromosomes, Human, Pair 14--Genetics--GE; DNA, Neoplasm; Gene
Expression Regulation,
Neoplastic--Genetics--GE; In Situ Hybridization, Fluorescence;
Karyotyping; Molecular
Sequence Data
CAS Registry No.: 0 (proto-oncogene protein bcl-6); 0 (DNA-Binding
Proteins); 0
(DNA, Neoplasm); 0 (Immunoglobulins); 0 (Proto-Oncogene Proteins);
0
(Transcription Factors)
48 Complete Record
99039811
Involvement of BCL6 in chromosomal aberrations affecting band 3q27 in
B-cell non-
Hodgkin lymphoma.
Chaganti SR; Chen W; Parsa N; Offit K; Louie DC; Dalla-Favera R;
Chaganti RS
Laboratory of Cancer Genetics, Sloan-Kettering Institute, Memorial
Sloan-Kettering
Cancer Center, New York, New York 10021, USA.
Genes, chromosomes & cancer (UNITED STATES) Dec 1998 23 (4) p323-7
ISSN: 1045-
2257 Contract/Grant No.: CA-66999--CA--NCI; CA-44029--CA--NCI
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9907
Subfile: INDEX MEDICUS
Chromosomal band 3q27 exhibits recurring and nonrecurring
translocations and other
rearrangements in approximately 8% of B-cell non-Hodgkin lymphomas (NHL)
belonging to
low-grade as well as diffuse aggressive histologies. The BCL6 gene,
which encodes a
zinc-finger transcription repressor protein and which maps to
chromosomal band 3q27,
is deregulated in t(3;14)(q27;q32) and other translocations by
substitution of its
transcription regulatory sequences by those of genes on the partner
chromosomes. To
delineate the cytogenetics and investigate the nature and consequence of
BCL6
involvement in the spectrum of 3q27 aberrations seen in NHL, we analyzed
a panel of
53 NHL tumors with 3q27 aberrations for BCL6 gene rearrangements and a
subset of 32
of these for mutations. We identified four new recurring translocations
involving
3q27, in addition to the previously recognized t(3;14)(q27;q32) and its
variant,
t(3;22)(q27;q11). Histologically, the 3q27 breaks were represented by
4% mantle cell
lymphomas, 38% follicular center cell lymphomas, and 58% diffuse large
B-cell
lymphomas. Approximately 50% of the tumors exhibited BCL6
rearrangements, whereas
87.5% showed mutations in the 5' noncoding region which contains the
transcription
regulatory sequences. These results demonstrate that a substantial
proportion of
cytogenetically detected 3q27 breaks in NHLs do not represent
BCL6-associated
translocations. They also suggest alternate breakpoints which may lead
to BCL6
deregulation, or involvement of other genes in 3q27 translocations. The
frequent
BCL6 mutation in these tumors is consistent with our previous
observation of
hypermutation of the 5' noncoding region of the gene in lymphomas
arising in the
germinal-center B-cells.
Tags: Human; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
Descriptors: *Chromosome Aberrations--Genetics--GE; *Chromosomes,
Human, Pair 3--
Genetics--GE; *DNA-Binding Proteins--Genetics--GE; *Lymphoma,
B-Cell--Genetics--GE;
*Lymphoma, Non-Hodgkin--Genetics--GE; *Proto-Oncogene
Proteins--Genetics--GE;
*Transcription Factors--Genetics--GE; *Zinc Fingers--Genetics--GE;
Chromosome Banding;
Chromosome Mapping; Chromosomes, Human, Pair 1--Genetics--GE;
Chromosomes, Human,
Pair 14--Genetics--GE; Chromosomes, Human, Pair 2--Genetics--GE;
Chromosomes, Human,
Pair 22--Genetics--GE; Chromosomes, Human, Pair 5--Genetics--GE;
Chromosomes, Human,
Pair 9--Genetics--GE; DNA, Neoplasm--Analysis--AN; Gene Expression
Regulation,
Neoplastic--Genetics--GE; Polymorphism, Single-Stranded Conformational;
Reverse
Transcriptase Polymerase Chain Reaction; Translocation
(Genetics)--Genetics--GE
CAS Registry No.: 0 (proto-oncogene protein bcl-6); 0 (DNA-Binding
Proteins); 0
(DNA, Neoplasm); 0 (Proto-Oncogene Proteins); 0 (Transcription
Factors)
58 Complete Record
99223160
Bcl-6 expression in reactive follicular hyperplasia, follicular
lymphoma, and
angioimmunoblastic T-cell lymphoma with hyperplastic germinal centers:
heterogeneity
of intrafollicular T-cells and their altered distribution in the
pathogenesis of
angioimmunoblastic T-cell lymphoma.
Ree HJ; Kadin ME; Kikuchi M; Ko YH; Suzumiya J; Go JH
Department of Diagnostic Pathology, Samsung Medical Center, Seoul,
Korea.
Human pathology (UNITED STATES) Apr 1999 30 (4) p403-11 ISSN:
0046-8177
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9907
Subfile: INDEX MEDICUS
BACKGROUND: The Bcl-6 gene product, a nuclear phosphoprotein, is
expressed
independently of Bcl-6 gene rearrangement. In lymph nodes, expression
of Bcl-6
protein is restricted to germinal center (GC) B-cells and 10% to 15% of
CD3/CD4+
intrafollicular T cells. Interfollicular cells are negative for Bcl-6
protein,
except for rare CD3+/CD4+ T cells. Recently, we reported cases of
angioimmunoblastic
T-cell lymphoma (AITL) with hyperplastic GCs (AITL/GC), and observed
that borders of
enlarged GCs were ill defined, with features suggestive of an outward
migration of GC
cells to surrounding interfollicular zones. This prompted a study of
follicular
borders with Bcl-6 staining in reactive follicular hyperplasias and
follicular
lymphomas to compare with AITL/GC. MATERIALS AND METHODS:
Formalin-fixed paraffin
sections were used for immunostaining of Bcl-6. Six cases of AITL/GC,
12 nonspecific
reactive follicular hyperplasia (FH), 7 HIV adenopathy, 10 follicular
lymphoma (FL),
and 8 typical AITL (ie, AITL without GC) were studied. Double staining
for Bcl-6/
CD20, Bcl-6/CD3, and Bcl-6/CD57 was performed in selected cases.
RESULTS: In FH and
HIV adenopathy, staining for Bcl-6 revealed densely populated GCs with
well-defined
and regular GC borders, whereas Bcl-6+ cells were rare in the
interfollicular areas.
An occasional GC with an ill-defined border was invariably surrounded by
a broad
mantle zone; those with indistinct mantle zones had well-defined,
regular borders.
In FL, follicles were densely populated, and their borders were
irregular, with some
Bcl-6+ cells in the interfollicular zones. In AITL/GC, GCs were less
dense, GC
borders were ill defined and irregular, and the number of
interfollicular Bcl-6+
cells was markedly increased. Double staining revealed that these
interfollicular
Bcl-6+ cells in AITL/GC were Bcl6+/CD3+/CD20-/CD57- T cells. Moreover,
CD3+
intrafollicular T cells were depleted in AITL/GC, whereas they were
abundant in FH.
Intrafollicular CD57+ cells did not stain for Bcl-6, and were also
depleted in AITL/
GC. In typical AITL, some neoplastic cells were positive for Bcl-6,
showing variable
degrees of staining. CONCLUSIONS: (1) GCs of AITL/GC differed from
those of other
reactive follicular hyperplasias and follicular lymphomas, and staining
for Bcl-6 was
useful to discern them. (2) Intrafollicular CD3+ T cells, many of which
were also
positive for Bcl-6, were markedly depleted in AITL/GC, with increased
interfollicular
Bcl-6+/CD3+ cells, suggesting an outward migration of intrafollicular T
cells in this
condition. (3) Interfollicular Bcl-6+/CD3+ cells in AITL/GC were too
numerous to be
accounted for by migration alone, suggesting local proliferation. (4)
Intrafollicular CD57+ cells were negative for Bcl-6, indicating
heterogeneity of the
intrafollicular T-cell population. (5) Some neoplastic cells in AITL
stained for Bcl-
6, suggesting up-regulation of Bcl-6 expression in this tumor.
Tags: Female; Human; Male; Support, Non-U.S. Gov't
Descriptors: *DNA-Binding Proteins--Biosynthesis--BI; *Lymphoma,
Follicular--
Metabolism--ME; *Lymphoma, T-Cell--Metabolism--ME; *Proto-Oncogene
Proteins--
Biosynthesis--BI; *Transcription Factors--Biosynthesis--BI; Adult;
Hyperplasia--
Metabolism--ME; T-Lymphocytes
CAS Registry No.: 0 (proto-oncogene protein bcl-6); 0 (DNA-Binding
Proteins); 0
(Proto-Oncogene Proteins); 0 (Transcription Factors)
66 Complete Record
99120219
Increased expression of the LAZ3 (BCL6) proto-oncogene accompanies
murine skeletal
myogenesis.
Albagli-Curiel O; Dhordain P; Lantoine D; Aurade F; Quief S; Kerckaert
JP;
Montarras D; Pinset C
INSERM U124, Onco-Hematologie Moleculaire, Lille, France.
Differentiation (GERMANY) Nov 1998 64 (1) p33-44 ISSN: 0301-4681
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9905
Subfile: INDEX MEDICUS
The structural alterations of the LAZ3 (BCL6) gene are one of the most
frequent
events found in non-Hodgkin lymphoma. LAZ3 encodes a transcriptional
repressor with
a POZ/zinc finger structure similar to several Drosophila development
regulators and
to the human promyelocytic leukemia-associated PLZF gene. Consistent
with the origin
of LAZ3-associated malignancies, LAZ3 is expressed in mature B-cells and
required for
germinal center formation. However, its ubiquitous expression, with
predominant
levels in skeletal muscle, suggests that it may act outside the lymphoid
system. To
study how LAZ3 could be involved in skeletal muscle differentiation, we
examined its
expression in the C2 muscle cells. We report here that LAZ3 is
upregulated at both
mRNA and protein levels during the differentiation of proliferating C2
myoblasts into
post-mitotic myotubes. This rise in LAZ3 expression is both precocious
and
sustained, and is not reversed when myotubes are re-exposed to
mitogen-rich medium,
suggesting that irreversible evens occurring upon myogenic terminal
differentiation
contribute to lock LAZ3 upregulation. In addition, using two different
models, we
found that a "simple" growth-arrest upon serum starvation is not
sufficient to induce
LAZ3 upregulation which rather appears as a feature of myogenic
commitment and/or
differentiation. Finally, BrdU incorporation assays in C2 cells
entering the
differentiation pathway indicate that "high" LAZ3 expression strongly
correlates with
their exit from the cell cycle. Taken as a whole, these findings
suggest that LAZ3
could play a role in muscle differentiation. Together with some results
reported in
other cell types, we propose that LAZ3 may contribute to events common
to various
differentiation processes, possibly the induction and stabilization of
the withdrawal
from the cell cycle.
Tags: Animal; Support, Non-U.S. Gov't
Descriptors: *DNA-Binding Proteins--Biosynthesis--BI; *Gene Expression
Regulation,
Developmental; *Muscle, Skeletal--Cytology--CY; *Proto-Oncogene
Proteins--
Biosynthesis--BI; *Proto-Oncogenes; *Transcription
Factors--Biosynthesis--BI; *Zinc
Fingers--Genetics--GE; Cell Differentiation; Cell Division; Cells,
Cultured; Culture
Media, Conditioned; DNA-Binding Proteins--Genetics--GE;
Fibroblasts--Cytology--CY;
Fibroblasts--Drug Effects--DE; Mice; Proto-Oncogene
Proteins--Genetics--GE; RNA,
Messenger--Biosynthesis--BI; Transcription Factors--Genetics--GE
CAS Registry No.: 0 (proto-oncogene protein bcl-6); 0 (Culture
Media,
Conditioned); 0 (DNA-Binding Proteins); 0 (Proto-Oncogene Proteins);
0 (RNA,
Messenger); 0 (Transcription Factors)
69 Complete Record
99142601
Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and
mutated in
multiple tumor types {see comments}
Willis TG; Jadayel DM; Du MQ; Peng H; Perry AR; Abdul-Rauf M; Price H;
Karran L;
Majekodunmi O; Wlodarska I; Pan L; Crook T; Hamoudi R; Isaacson PG; Dyer
MJ
Academic Department of Haematology and Cytogenetics, Institute of
Cancer Research,
Sutton, Surrey, United Kingdom.
Cell (UNITED STATES) Jan 8 1999 96 (1) p35-45 ISSN: 0092-8674
Note: Comment in: Cell 1999 Jun 11;97(6):683-4; discussion 686-8;
Comment in: Cell
1999 Jun 11;97(6):684-6; discussion 686-8
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9905
Subfile: INDEX MEDICUS
MALT B cell lymphomas with t(1;14)(p22;q32) showed a recurrent
breakpoint upstream
of the promoter of a novel gene, Bcl10. Bcl10 is a cellular homolog of
the equine
herpesvirus-2 E10 gene: both contain an amino-terminal caspase
recruitment domain
(CARD) homologous to that found in several apoptotic molecules. Bcl10
and E10
activated NF-kappaB but caused apoptosis of 293 cells. Bcl10 expressed
in a MALT
lymphoma exhibited a frameshift mutation resulting in truncation distal
to the CARD.
Truncated Bcl10 activated NF-kappaB but did not induce apoptosis.
Wild-type Bcl10
suppressed transformation, whereas mutant forms had lost this activity
and displayed
gain-of-function transforming activity. Similar mutations were detected
in other
tumor types, indicating that Bcl10 may be commonly involved in the
pathogenesis of
human malignancy.
Tags: Animal; Human; Support, Non-U.S. Gov't
Descriptors: *Chromosomes, Human, Pair 1; *Chromosomes, Human, Pair
14; *Lymphoma,
Mucosa-Associated Lymphoid Tissue--Genetics--GE; *Mutation; *Neoplasm
Proteins--
Genetics--GE; *Translocation (Genetics); Amino Acid Sequence; Apoptosis;
Base
Sequence; Cell Line, Transformed; Cell Transformation, Neoplastic;
Cloning, Molecular;
COS Cells; Gene Expression; Hela Cells; Mice; Molecular Sequence Data;
Neoplasm
Proteins--Physiology--PH; Neoplasms--Genetics--GE; NF-kappa
B--Metabolism--ME;
Sequence Homology, Amino Acid
Molecular Sequence Databank No.: GENBANK/AJ006288; GENBANK/AJ006289
CAS Registry No.: 0 (Bcl10 protein); 0 (Neoplasm Proteins); 0
(NF-kappa B)
84 Complete Record
99047247
Variants of B cell lymphoma 6 (BCL6) and marked atopy {letter}
Adra CN; Gao PS; Mao XQ; Baron BW; Pauker S; Miki T; Shirakawa T;
Hopkin JM
Clinical genetics (DENMARK) Oct 1998 54 (4) p362-4 ISSN: 0009-9163
Contract/Grant No.: R29 AI 43663-01--AI--NIAID
Language: ENGLISH
Document Type: LETTER
Journal Announcement: 9903
Subfile: INDEX MEDICUS
Tags: Human; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
Descriptors: *Asthma--Genetics--GE; *Dermatitis, Atopic--Genetics--GE;
*DNA-Binding
Proteins--Genetics--GE; *Proto-Oncogene Proteins--Genetics--GE;
*Transcription
Factors--Genetics--GE; Asthma--Etiology--ET; Asthma--Immunology--IM;
Dermatitis,
Atopic--Etiology--ET; Dermatitis, Atopic--Immunology--IM;
IgE--Metabolism--ME;
Variation (Genetics)
CAS Registry No.: 0 (proto-oncogene protein bcl-6); 0 (DNA-Binding
Proteins); 0
(Proto-Oncogene Proteins); 0 (Transcription Factors); 37341-29-0
(IgE)
88 Complete Record
99043627
FISH detection of chromosome 14q32/IgH translocations: evaluation in
follicular
lymphoma.
Rack KA; Salomon-Nguyen F; Radford-Weiss I; Gil MO; Schmitt C;
Belanger C; Nusbaum
S; Vekemans M; Valensi F; Macintyre EA
Department of Biological Haematology, Hopital Necker-Enfants Malades,
Paris,
France.
British journal of haematology (ENGLAND) Nov 1998 103 (2) p495-504
ISSN: 0007-
1048
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9903
Subfile: INDEX MEDICUS
A FISH strategy capable of detecting chromosome 14q32 rearrangements
involving the
IgH locus, including in interphase nuclei, was developed using Ig
variable and
constant region cosmids from the extremities of the locus in a dual
hybridization
approach, using signal splitting as evidence of rearrangement. The
large size of the
locus (1.3 Mb) and the propensity for internal deletion due to
physiological VDJ
recombination and isotype switching complicate analysis of this locus.
We used the
Ig10 cosmid, which hybridizes to C epsilon and C alpha2 at the 3' end of
the constant
region, in order to minimize deletion and/or splitting of the constant
region probe.
Cos Ig10 and the IgV18 VH probes were compared with a specific IgH-BCL2
FISH dual
hybridization approach in follicular lymphoma (FL). Both were capable
of detecting
the t(14;18) in interphase nuclei, including in cases with no apparent
abnormality by
classic karyotype analysis, although the sensitivity of the IgH approach
was slightly
lower. We have also successfully applied these probes to whole cell
cytospin
preparations, rendering analysis of cryopreserved material possible,
although
interpretation should be limited to frequent events, particularly
following cell
manipulation. Analysis of flow cytometric sorted bone marrow fractions
from three FL
patients by FISH and FICTION showed that the t(14;18) was present in a
much lower
proportion of CD34 positive than negative cells but that the higher
level of
background hybridization limits use of these techniques for the reliable
quantification of rare events.
Tags: Human; Support, Non-U.S. Gov't
Descriptors: *Chromosomes, Human, Pair 14; *Immunoglobulins,
Heavy-Chain--Genetics--
GE; *Lymphoma, Follicular--Genetics--GE; *Translocation (Genetics); Cell
Separation;
Chromosomes, Human, Pair 18; Flow Cytometry; Genes, bcl-2; In Situ
Hybridization,
Fluorescence; Interphase; Karyotyping; Metaphase
CAS Registry No.: 0 (Immunoglobulins, Heavy-Chain)
92 Complete Record
99005342
Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse
large B-cell
lymphoma.
Kramer MH; Hermans J; Wijburg E; Philippo K; Geelen E; van Krieken JH;
de Jong D;
Maartense E; Schuuring E; Kluin PM
Departments of Pathology and Medical Statistics, Leiden University
Medical Center,
Leiden, The Netherlands.
Blood (UNITED STATES) Nov 1 1998 92 (9) p3152-62 ISSN: 0006-4971
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9902
Subfile: AIM; INDEX MEDICUS
Diffuse large B-cell lymphoma (DLCL) is characterized by a marked
degree of
morphologic and clinical heterogeneity. We studied 156 patients with de
novo DLCL
for rearrangements of the BCL2, BCL6, and MYC oncogenes by Southern blot
analysis and
BCL2 protein expression. We related these data to the primary site of
presentation,
disease stage, and other clinical risk factors. Structural alterations
of BCL2, BCL6
, and MYC were detected in 25 of 156, 36 of 116, and 10 of 151 patients,
respectively.
Three cases showed a combination of BCL2 and BCL6 rearrangements, and
two cases had a
combination of BCL6 and MYC rearrangements. BCL2 rearrangement was
found more often
in extensive (39%) and primary nodal (17%) lymphomas than in extranodal
cases (4%) (P
= .003). BCL2 rearrangement was present in none of 40 patients with
stage I disease,
but in 22% of patients with stage II to IV (P = .006). The presence of
BCL2
rearrangements did not significantly affect overall survival (OS) or
disease-free
survival (DFS). In contrast, high BCL2 protein expression adversely
affected both OS
(P = .008) and DFS (P = .01). BCL2 protein expression was poorly
correlated with
BCL2 rearrangement: only 52% of BCL2-rearranged lymphomas and 37% of
BCL2-
unrearranged cases had high BCL2 protein expression. Rearrangement of
BCL6 was found
more often in patients with extranodal (36%) and extensive (39%)
presentation versus
primary nodal disease (28%). No significant correlation was found with
disease
stage, lymphadenopathy, or bone marrow involvement. DFS and OS were not
influenced
by BCL6 rearrangements. MYC rearrangements were found in 16% of primary
extranodal
lymphomas, versus 2% of primary nodal cases (P = .02). In particular,
gastrointestinal (GI) lymphomas (5 of 18 cases, 28%) were affected by
MYC
rearrangements. The distinct biologic behavior of these extranodal
lymphomas was
reflected by a high complete remission (CR) rate: 7 of 10 patients with
MYC
rearrangement attained complete remission and 6 responders remained
alive for more
than 4 years, resulting in a trend for better DFS (P = .07). These data
show the
complex nature of molecular events in DLCL, which is a reflection of the
morphologic
and clinical heterogeneity of these lymphomas. However, thus far, these
genetic
rearrangements fail as prognostic markers. Copyright 1998 by The
American Society of
Hematology
Tags: Human; Support, Non-U.S. Gov't
Descriptors: *DNA-Binding Proteins--Genetics--GE; *Genes, bcl-2;
*Genes, myc;
*Lymphoma, B-Cell--Genetics--GE; *Lymphoma, Large-Cell,
Diffuse--Genetics--GE;
*Oncogenes; *Proto-Oncogene Proteins--Genetics--GE; *Transcription
Factors--Genetics--
GE; Blotting, Southern; Disease-Free Survival; DNA Mutational Analysis;
DNA, Neoplasm-
-Genetics--GE; Gastrointestinal Neoplasms--Genetics--GE;
Gastrointestinal Neoplasms--
Mortality--MO; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Genes,
Immunoglobulin;
Immunoglobulins, Heavy-Chain--Genetics--GE; Life Tables; Lymphoma,
B-Cell--Mortality--
MO; Lymphoma, Large-Cell, Diffuse--Mortality--MO; Neoplasm
Proteins--Biosynthesis--BI;
Neoplasm Proteins--Genetics--GE; Netherlands; Prognosis; Proto-Oncogene
Proteins c-
bcl-2--Biosynthesis--BI; Remission Induction; Survival Rate
CAS Registry No.: 0 (proto-oncogene protein bcl-6); 0 (DNA-Binding
Proteins); 0
(DNA, Neoplasm); 0 (Immunoglobulins, Heavy-Chain); 0 (Neoplasm
Proteins); 0
(Proto-Oncogene Proteins c-bcl-2); 0 (Proto-Oncogene Proteins); 0
(Transcription
Factors)
96 Complete Record
99010724
The t(2;3)(q21;q27) translocation in non-Hodgkin's lymphoma displays
BCL6 mutations
in the 5' regulatory region and chromosomal breakpoints distant from the
gene.
Chen W; Butler M; Rao PH; Chaganti SR; Louie DC; Dalla-Favera R;
Chaganti RS
Department of Human Genetics, Memorial Sloan-Kettering Cancer Center,
New York, NY
10021, USA.
Oncogene (ENGLAND) Oct 1 1998 17 (13) p1717-22 ISSN: 0950-9232
Contract/Grant No.: CA66999--CA--NCI; CA44029--CA--NCI
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9901
Subfile: INDEX MEDICUS
The BCL6 gene, mapped at the chromosomal band 3q27, encodes a POZ/Zinc
finger
transcription repressor protein. It is frequently activated in
Non-Hodgkin's
lymphomas (NHL) by translocations with breakpoints clustering in the 5'
major
breakpoint region (MBR) as well as by mutations in the same region. The
translocations lead to BCL6 activation by substitution of promoters of
rearranging
genes derived from the reciprocal chromosomal partners such as IG. We
report the
molecular genetic analysis of a novel t(2;3)(q21;q27) translocation
subset in NHL
comprising three cases without apparent BCL6 involvement in the
translocation.
Southern blot analysis of tumor DNAs utilizing BCL6 MBR probes revealed
no
rearrangement in two cases. Two rearranged bands in the third case
resulted from a
deletion in one allele and a mutation in the other allele. Southern
blot analysis of
DNA from one of the two tumors without BCL6 rearrangement, using a probe
derived from
the recently identified alternative breakpoint region (ABR), showed a
rearrangement.
The ABR is located 200-270 kb telomeric to MBR. Mutations were
identified in the
previously reported hypermutable region of BCL6 in all three tumors. In
one, the
mutant allele alone was found to be expressed by RT-PCR analysis of RNA.
These
results demonstrate the presence of 3q27 translocation breakpoints at a
distance from
BCL6 suggesting distant breaks that deregulate the gene or involvement
of other genes
that may be subject to rearrangement.
Tags: Human; Male; Support, U.S. Gov't, P.H.S.
Descriptors: *Chromosomes, Human, Pair 2; *Chromosomes, Human, Pair 3;
*DNA-Binding
Proteins--Genetics--GE; *Lymphoma, Non-Hodgkin--Genetics--GE; *Mutation;
*Proto-
Oncogene Proteins--Genetics--GE; *Regulatory Sequences, Nucleic Acid;
*Transcription
Factors--Genetics--GE; *Translocation (Genetics); Alleles; Blotting,
Southern;
Chromosome Breakage; Gene Rearrangement; Middle Age; Polymerase Chain
Reaction;
Polymorphism, Single-Stranded Conformational
CAS Registry No.: 0 (proto-oncogene protein bcl-6); 0 (DNA-Binding
Proteins); 0
(Proto-Oncogene Proteins); 0 (Transcription Factors)