CDKN2A is not the principal target of deletions on the short arm of chromosome 9 in neuroendocrine (Merkel cell) carcinoma of the skin

The majority of small-cell lung cancers (SCLCs) express p16 but not pRb, Gi ven our previous study showing loss of pRb in Merkel cell carcinoma (MCC)/n euroendocrine carcinoma of the skin and the clinicopathological similaritie s between SCLC acid MCC, we wished to determine if this was also the case i n MCC, Twenty-nine MCC specimens from 23 patients were examined for deletio ns at 10 loci on 9p and I on 9p. No loss of heterozygosity (LO H) was peen in 9 patients including 2 for which tumour and cell line DNAs were examined . Four patients had LOH for all informative loci on 9p, Ten tumours showed more limited regions of loss on 9p, and from these 2 common regions of dele tion were determined, Half of all informative cases had LOH at D95168, the most telomeric marker examined, and 3 specimens showed loss of only D9S168, A second region (InFNA-D9S126) showed L0H in 10(44%) cases, and case MCC26 showed LOH for only D9S126, implicating genes centromeric of the CDKN2A lo cus. No mutations in the coding regions of p16 were seen in 7 cell lines te sted, and reactivity to anti-p16 antibody was seen in all Il tumour specime ns examined and in 6 of 7 cell lines from 6 patients. Furthermore, all cell lines examined reacted with anti-p 14""' antibody, These results suggest t hat neither transcript of the CDKN2A locus is the target of deletions on 9p in MCC and imply the existence of tumour-suppressor genes mapping both cen tromeric and telomeric of this locus. (C) 2001 Wiley-Liss, Inc.