Chromosomal and gene amplification in diffuse large B-cell lymphoma Journal Article

Authors: Rao, P. H.; Houldsworth, J.; Dyomina, K.; Parsa, N. Z.; Cigudosa, J. C.; Louie, D. C.; Popplewell, L.; Offit, K.; Jhanwar, S. C.; Chaganti, R. S. K.
Article Title: Chromosomal and gene amplification in diffuse large B-cell lymphoma
Abstract: Chromosomal translocations leading to deregulation of specific oncogenes characterize approximately 50% of cases of diffuse large B-cell lymphomas (DLBL). To characterize additional genetic features that may be of value in delineating the clinical characteristics of DLBL, we studied a panel of 96 cases at diagnosis consecutively ascertained at the Memorial Sloan-Kettering Cancer Center (MSKCC) for incidence of gene amplification, a genetic abnormality previously shown to be associated with tumor progression and clinical outcome. A subset of 20 cases was subjected to comparative genomic hybridization (CGH) analysis, which identified nine sites of chromosomal amplification (1q21-23, 2p12-16, 8q24, 9q34, 12q12-14, 13q32, 16p12, 18q21- 22, and 22q12). Candidate amplified genes mapped to these sites were selected for further analysis based on their known roles in lymphoid cell and lymphoma development, and/or history of amplification in tumors. Probes for six genes, which fulfilled these criteria, REL (2p12-16), MYC (8q24), BCL2 (18q21), GLI, CDK4, and MDM2 (12q13-14), were used in a quantitative Southern blotting analysis of the 96 DLBL DNAs. Each of these genes was amplified (four or more copies) with incidence ranging from 11% to 23%. This analysis is consistent with our previous finding that REL amplification is associated with extranodal presentation. In addition, BCL2 rearrangement and/or REL, MYC, BCL2, GLI, CDK4, and MDM2 amplification was associated with advanced stage disease. These data show, for the first time, that amplification of chromosomal regions end genes is a frequent phenomenon in DLBL and demonstrates their potential significance in lymphomagenesis.
Keywords: human tissue; human cell; gene amplification; b lymphocyte; gene mapping; oncogene; lymphoma, b-cell; chromosome translocation; translocation, genetic; large cell lymphoma; chromosome analysis; chromosomes, human; chromosome mapping; hybridization; southern blotting; lymphoma, large-cell, diffuse; humans; human; priority journal; article
Journal Title: Blood
Volume: 92
Issue: 1
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 1998-07-01
Start Page: 234
End Page: 240
Language: English
PUBMED: 9639522
PROVIDER: scopus
Notes: Article -- Export Date: 12 December 2016 -- Source: Scopus