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

• Published in: Human molecular genetics Vol. 10; no. 1; pp. 55 - 62
• Main Authors: Randerson-Moor, JA, Harland, M, Williams, S, Cuthbert-Heavens, D, Sheridan, E, Aveyard, J, Sibley, K, Whitaker, L, Knowles, M, Bishop, J N, Bishop, D T
• Format: Journal Article
• Language: English
• Published: 01.01.2001
• Subjects: CDKN2A gene; CDKN2B gene; melanoma-astrocytoma syndrome; p14ARF gene; p16 protein
• ISSN: 0964-6906

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