CDKN2 explains part of the clinical phenotype in Dutch familial atypical multiple-mole melanoma (FAMMM) syndrome families.
Combined multi-point linkage analysis in seven Dutch families with FAMMM syndrome confirmed the location of a melanoma susceptibility (MLM) gene in the 9p21 area. The occurrence of a shared high-risk haplotype in six of the families strongly suggests a founder effect in the Leiden region. No indication for locus heterogeneity was observed. Recently, the CDKN2 (p16) gene, an important regulator of the cell cycle, was isolated from the 9p21 region. A 19-bp germline deletion in the CDKN2 gene was detected in the high-risk haplotype, suggesting CDKN2 to be identical to MLM. Loss of heterozygosity studies in melanoma and pancreatic carcinoma from gene carriers strongly support the view that CDKN2 is a general tumour suppressor gene predisposing not only to melanoma but also to other malignancies. Interestingly, the occurrence of apparent clinical FAMMM cases with melanoma but without the high-risk deletion haplotype suggests the necessity of additional (naevus) genes to explain the complete FAMMM phenotype.
Gruis
N A
NA
MGC-Department of Human Genetics, Leiden University, The Netherlands.
Sandkuijl
L A
LA
van der Velden
P A
PA
Bergman
W
W
Frants
R R
RR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004247:DNA / Q000032:analysis; D005260:Female; D018703:Founder Effect; D016147:Genes, Tumor Suppressor; D018095:Germ-Line Mutation; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009426:Netherlands; D010375:Pedigree; D010641:Phenotype
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004247:DNA