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)