Similar patterns of genomic alterations characterize primary mediastinal large-B-cell lymphoma and diffuse large-B-cell lymphoma

Nallasivam Palanisamy, Ashraf A. Abou-Elella, Seeta R. Chaganti, Jane Houldsworth, Kenneth Offit, Diane C. Louie, Julie Terayu-Feldstein, Juan C. Cigudosa, Pulivarthi H. Rao, Warren G. Sanger, Dennis D. Weisenburger, R. S.K. Chaganti

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

To address the possible genetic relationship between primary mediastinal large-B-cell lymphoma (PMLBCL) and diffuse large-B-cell lymphoma (DLBCL), we compared DNA copy number changes identified by comparative genomic hybridization (CGH) analysis of 40 PMLBCL and 91 DLBCL tumors. We assessed their karyotypes by G-banding; amplification of MYC, BCL2, and REL genes by Southern blotting; and incidence of nonpolymorphic BCL6 mutations by single-strand conformation polymorphism analysis (SSCP). Overall, CGH identified overlapping and nonoverlapping patterns of DNA copy number changes in the two groups. Among the latter changes, gains of chromosomes 8, 11, 15, and 16 and losses of chromosomes 5, 10, 15, 16, 17, and 20 were seen only in DLBCL, and gains of chromosomes 10, 21, and 22 and losses of chromosomes 11, 13, and 18 were seen only in PMLBCL. Several overlapping changes were identified in both groups, with variation in incidence. Statistical analysis of these changes showed significant gains of chromosomes 3 (P ≤ 0.05) and 7q (P ≤ 0.05) in DLBCL and gains of chromosomes 9 (P ≤ 0.05) and 19 (P ≤ 0.05) and the X chromosome (P ≤ 0.05) and loss of chromosome 4 (P ≤ 0.05) in PMLBCL. Frequent recurring DNA amplification at 2p13-15 and less frequent amplification at 6p21, 12q13, and 18q21 were noted in both groups. Recurring amplification at 1q21 was seen only in DLBCL, whereas nonrecurring amplification at 10p11.2 and 15q22-24 was seen only in PMLBCL. G-banded karyotype analysis identified t(3;14)(q27;q32) in one and t(14;18)(q32;q21) in two cases of PMLBCL. Seven of 13 cases exhibited SSCP variants in the 5′ noncoding region of BCL6. In addition, 19 of 24 PMLBCLs assayed for BCL6 protein expression by immunohistochemistry showed positive results, indicating an origin from a germinal center (GC)-derived B cell. Based on these data, we conclude that PMLBCL is a distinct entity among GC-derived high-grade DLBCLs.

Original languageEnglish (US)
Pages (from-to)114-122
Number of pages9
JournalGenes Chromosomes and Cancer
Volume33
Issue number2
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'Similar patterns of genomic alterations characterize primary mediastinal large-B-cell lymphoma and diffuse large-B-cell lymphoma'. Together they form a unique fingerprint.

Cite this