CONSTITUTIONAL ALTERATIONS IN P16 IN PATIENTS WITH UVEAL MELANOMA

Chromosome 9p21 contains a susceptibility gene for cutaneous melanoma. Recent studies suggest that the gene responsible may be CDK41, since it encodes a putative cell cycle inhibitor, p16, and is frequently los t or rearranged in melanoma cell lines. In this study we examined whet her germline alterations in CDK41 could be identified in patients with melanoma of the uveal tract. From an archive of bloods collected from patients with uveal melanoma, we identified 13 samples drawn from pat ients with a history in a family member of uveal (n = 6) or cutaneous (n = 7) melanoma. An additional 24 'control' bloods (without melanoma or any other primary malignancy in a family member), similar to the 'c ases' in age end number of first-degree relatives, were also selected for study. For each sample, DNA was extracted from the red blood cell fraction. Using the polymerase chain reaction-single strand conformati on polymorphism method, we screened for alterations in p16. Specific c hanges were characterized by DNA sequencing. Six nucleotide changes we re detected In five (13.5%) of the 37 samples examined. An altered gen e was found in one (7.7%) of the 13 patients with a family history (of intra-ocular melanoma) and four (16.7%) of the 24 patients with no fa mily history (P = 0.64) of melanoma. In this series the group with a p ositive family history was predominantly female and most pedigrees inv olved matrilineal descent. In these data prevalence of germline altera tion in p16 was similar in familial and sporadic cases. The results pr ovide evidence against a significant role for p16 in familial clusteri ng of intra-ocular and cutaneous melanomas.