A germline deletion of p14(ARF) but not CDKN2A in a melanoma-neural systemtumour syndrome family

The melanoma-astrocytoma syndrome is characterized by a dual predisposition to melanoma and neural system tumours, commonly astrocytoma. Germline dele tions of the region on 9p21 containing the CDKN2A and CDKN2B genes and CDKN 2A exon 1 beta have been reported in kindreds, implicating contiguous tumou r suppressor gene deletion as a cause of this syndrome. We describe a famil y characterized by multiple melanoma and neural cell tumours segregating wi th a germline deletion of the p14(ARF)-specific exon 1 beta of the CDKN2A g ene. This deletion does not affect the coding or minimal promoter sequences of either the CDKN2A or CDKN2B genes. Our results are consistent with eith er: (i) loss of p14(ARF) function being the critical abnormality associated with this syndrome, rather than contiguous loss of both the CDKN2A and CDK N2B genes as suggested previously; or (ii) disruption of expression of p16 by mechanisms as yet unknown.