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


Authors: Palanisamy, N.; Abou-Elella, A. A.; Chaganti, S.; Houldsworth, J.; Offit, K.; Louie, D. C.; Teruya-Feldstein, J.; Cigudosa, J. C.; Rao, P. H.; Sanger, W. G.; Weisenburger, D. D.; Chaganti, R. S. K.
Article Title: Similar patterns of genomic alterations characterize primary mediastinal large-B-cell lymphoma and diffuse large-B-cell lymphoma
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. © 2002 Wiley-Liss, Inc.
Keywords: adolescent; adult; clinical article; human tissue; protein expression; aged; aged, 80 and over; middle aged; gene mutation; mutation; dna-binding proteins; proto-oncogene proteins; gene amplification; transcription factors; b cell lymphoma; lymphoma, b-cell; dna; gene rearrangement; x chromosome; protein bcl 6; chromosome aberrations; gene dosage; nucleic acid hybridization; chromosome 8; mediastinal neoplasms; chromosome loss; karyotype; chromosome 11; chromosome 1q; chromosome 17; chromosome 12q; oncogene myc; chromosome 7q; mediastinum lymph node; chromosome 15q; chromosome 18q; chromosome 16; chromosome 20; polymorphism, single-stranded conformational; chromosome banding; chromosome 2p; chromosome 6p; proto-oncogene proteins c-bcl-6; lymphoma, large-cell, diffuse; lymphoma, large-cell; chromosome 10p; humans; human; male; female; priority journal; article
Journal Title: Genes Chromosomes and Cancer
Volume: 33
Issue: 2
ISSN: 1045-2257
Publisher: Wiley Periodicals, Inc  
Date Published: 2002-02-01
Start Page: 114
End Page: 122
Language: English
DOI: 10.1002/gcc.10016
PUBMED: 11793437
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 14 November 2014 -- Source: Scopus
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MSK Authors
  1. Pulivarth H Rao
    66 Rao
  2. Kenneth Offit
    788 Offit
  3. Diane C Louie
    52 Louie
  4. Julie T Feldstein
    297 Feldstein
  5. Raju S K Chaganti
    391 Chaganti