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REL proto-oncogene is frequently amplified in extranodal diffuse large cell
lymphoma
J Houldsworth, S Mathew, PH Rao, K Dyomina, DC Louie, N Parsa, K Offit and RS Chaganti
Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center,
New York, NY 10021, USA.
Comparative genomic hybridization (CGH) analysis of DNA extracted from a
diffuse lymphoma with a large cell component (DLLC) that displayed double
minute chromosomes upon conventional karyotypic analysis indicated overt
amplification of DNA sequences derived from the 2p13-15 region. Southern
blot analysis of this tumor DNA with a cDNA probe for the proto-oncogene
REL, previously mapped to 2p14-15, indicated a greater than 35-fold
amplification of REL. To determine the incidence of REL amplification and
possible clinical or histologic association with DLLC, a panel of 111 tumor
DNAs from DLLC specimens was screened for REL amplification by Southern
blot analysis. A copy number of > or = 4 was noted in 26 cases (23%).
Southern blot analysis of these 26 tumor DNAs with a cDNA probe for TGFA,
mapped to 2p13, indicated lack of coamplification except in one case.
Another member of the Rel/NF- kappa B family of transcriptional activators,
RELA/p65 mapped to 11q13, was amplified in five cases as determined by
Southern blot analysis using a cDNA probe. Nineteen of the 26 DLLC (73%)
with REL amplification were primary extranodal lymphomas. As a group, the
tumors with REL amplification demonstrated an increased frequency of
chromosomal aberrations previously associated with tumor progression,
suggesting an oncogenic effect of amplified REL in B-lymphoid cells that
already contained a transforming genetic lesion. Thus, REL amplification is
a frequent event in DLLC, and probably constitutes a progression-associated
marker of primary extranodal lymphomas. This study shows the usefulness of
the CGH technique in identifying chromosomal regions overrepresented in
tumors that can point to amplified genes and may be correlated with
clinical features of the disease.
Volume 87,
Issue 1,
pp. 25-29,
01/01/1996
Copyright © 1996 by The American Society of Hematology
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