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Codeletion of CDKN2 and MTAP genes in a subset of non‐Hodgkin's lymphoma may be associated with histologic transformation from low‐grade to diffuse large‐cell lymphoma
Author(s) -
Dreyling Martin H.,
Roulston Diane,
Bohlander Stefan K.,
Vardiman James,
Olopade Olufunmilayo I.
Publication year - 1998
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/(sici)1098-2264(199805)22:1<72::aid-gcc10>3.0.co;2-k
Subject(s) - cdkn2a , mycosis fungoides , contig , lymphoma , biology , fluorescence in situ hybridization , cdkn2b , cancer research , anaplastic large cell lymphoma , cosmid , pathology , gene , chromosome , genetics , medicine , immunology , genome
Identifying the various genetic alterations that contribute to lymphomagenesis is key to our improved understanding of the biological behavior of the disease. Recently, we and others have defined a tumor suppressor region on the short arm of chromosome 9 harboring a cluster of genes, including MTAP , CDKN2A ( p16 INK4a ), and CDKN2B ( p15 INK4B ), which is frequently deleted in a variety of tumor types. To determine whether this region is involved in a particular subset of malignant lymphomas, we have examined 16 cases of diffuse large‐cell lymphoma (DLCL) (including three cases that evolved from low‐grade non‐Hodgkin lymphoma (NHL) (transformed DLCL)), and nine cases of low‐grade NHL that had subpopulations of large cells with a diffuse growth pattern (seven follicular NHL, one chronic lymphocytic leukemia, one mycosis fungoides). Interphase fluorescence in situ hybridization was performed on these samples using a 250‐kb cosmid contig (COSp16), which encompasses MTAP, CDKN2A , and CDKN2B . Six of the 16 DLCLs and one of nine low‐grade NHLs had deletions of COSp16. COSp16 was homozygously deleted in four cases; two cases had hemizygous deletions, and one case had a partial homozygous deletion of the cosmid contig. Three of 13 cases of de novo DLCL, all three transformed DLCLs, and one of nine low‐grade NHL had COSp16 deletions. Although the numbers are small, COSp16 deletion was associated with transformed DLCL in contrast to de novo DLCL ( P < 0.04, Fisher's exact test) or low‐grade NHL ( P < 0.02). The COSp16 deletion was mostly submicroscopic and was not observed in association with any specific recurring cytogenetic abnormalities. These results suggest that targeted deletion of the CDKN2A region occurs in a subset of non‐Hodgkin's lymphomas, and may be associated with transformed lymphomas. Genes Chromosomes Cancer 22:72–78, 1998. © 1998 Wiley‐Liss, Inc.