Germline CDKN2A mutation implicated in predisposition to multiple myeloma

Germline mutations of the CDKN2A (p16(INK4A)) tumor suppressor gene predisp ose patients to melanoma and pancreatic carcinoma. In contrast, mutations o f the murine CDKN2A gene predispose BALB/c mice to pristane-induced plasmac ytoma, We describe here a family in which a germline mutation of CDKN2A is present in 4 individuals who developed melanoma as well as in a fifth famil y member who is suffering from multiple myeloma, To determine whether the C DKN2A mutation predisposed the myeloma patient to her disease, we carried o ut loss of heterozygosity studies on sorted bone marrow from this individua l and observed loss of the wild type CDKN2A allele in the malignant plasma cells. We suggest that germline mutations of CDKN2A may predispose individu als to a wider variety of malignancy than has been hitherto reported, but t hat the expression of these cancers may depend heavily on the genetic backg round of the patient. (C) 2000 by The American Society of Hematology.