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
✍ Scribed by Martin H. Dreyling; Diane Roulston; Stefan K. Bohlander; James Vardiman; Olufunmilayo I. Olopade
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 209 KB
- Volume
- 22
- Category
- Article
- ISSN
- 1045-2257
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✦ Synopsis
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 Ͻ 0.04, Fisher's exact test) or low-grade NHL (P Ͻ 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.