Homozygotes for CDKN2 (p16) germline mutation in Dutch familial melanoma kindreds.
Nat Genet
; 10(3): 351-3, 1995 Jul.
Article
en En
| MEDLINE
| ID: mdl-7670475
ABSTRACT
The p16 gene (CDKN2) which is localized on chromosome 9p21, is deleted in a significant number of sporadic cancers. Moreover, germline mutations identified in some melanoma-prone kindreds last year suggested that CDKN2 is identical to the 9p21-linked melanoma susceptibility gene (MLM); however, failure to identify p16 mutations in all melanoma kindreds putatively linked to 9p21 left some doubts. We have analysed CDKN2 coding sequences in 15 Dutch familial atypical multiple mole-melanoma (FAMMM) syndrome pedigrees, and identified a 19 basepair (bp) germline deletion in 13 of them. All 13 families originate from an endogamous population. The deletion causes a reading frame shift, predicted to result in a severely truncated p16 protein. Interestingly, two family members are homozygous for the deletion, one of whom shows no obvious signs of disease. This surprising finding demonstrates that homozygotes for this CDKN2 mutation are viable, and suggests the presence of a genetic mechanism that can compensate for the functional loss of p16. Our results also greatly strengthen the notion that p16 is indeed MLM.
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Banco de datos:
MEDLINE
Asunto principal:
Mutación de Línea Germinal
/
Melanoma
/
Neoplasias Primarias Múltiples
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
/
Male
País/Región como asunto:
Europa
Idioma:
En
Revista:
Nat Genet
Asunto de la revista:
GENETICA MEDICA
Año:
1995
Tipo del documento:
Article
País de afiliación:
Países Bajos