DELETION OF CYCLIN-DEPENDENT KINASE-4 INHIBITOR GENES P15 AND P16 IN NON-HODGKINS-LYMPHOMA

B-cell non-Hodgkin's lymphoma (NHL) is a heterogeneous lymphoid malign ancy consisting of several histologic types. Alterations in proto-onco genes caused by reciprocal chromosome translocations have been implica ted in the etiology of specific histologic groups. In this study, we e xamined the contribution of the cell cycle inhibitor genes P15, P16, a nd P18 to pathogenesis in a large panel of 209 cytogenetically charact erized B-cell NHL tumors representing varied histologic groups. We ide ntified the homozygous deletion of P15 and P16 genes in 13 tumors from 12 patients, all belonging to diffuse large-cell histology; 10 had th is diagnosis made on presentation, 1 had transformed from small lympho cytic lymphoma, and 1 had transformed from Hodgkin's disease. Tumor-sp ecific point mutations were not identified in the coding regions of th ese genes. Cytogenetically, chromosome 9p was normal in all but one tu mor. On the other hand, eight tumors hemizygous for 99 by cytogenetic analysis showed wild-type configuration of these genes. Our study, the refore, indicates that deletion of P15 and P16 occurs in about 15% of diffuse large-cell NHL and is not usually detected by cytogenetic anal ysis. P18 was wild-type in all tumors including the 13 tumors hemizygo us for 1p. (C) 1995 by The American Society of Hematology.