title: Mutation analysis of candidate genes in melanoma-prone families: evidence of different pathogenetic mechanisms at chromosome 9P21.
abstract: Putative tumour suppressor genes CDKN2A and CDKN2B (on chromosome 9p21) and CDKN2A-interacting cell growth regulatory genes CDK4 and Id-1 have been demonstrated to be involved in the pathogenesis of malignant melanoma (MM). Mutation analysis of these candidate genes was performed in MM families from southern Italy with three or more affected members or two affected members and one or more relative with histologically diagnosed atypical naevus. Two CDKN2A mutations, Arg24Pro and 1-292 G>A, were observed in two (15%) families; except for CDKN2A and Id-1 polymorphisms, no sequence variations were detected in the remaining genes. Screening among 119 sporadic MM cases revealed two additional CDKN2A mutations at very low prevalences. Identification of a large shared haplotype at 9p21 in some MM families negative for CDKN germline mutations suggests that other CDKN-inactivating mechanisms may be responsible for MM predisposition or, alternatively, additional susceptibility gene(s) may be present on chromosome 9p21. Fluorescence in situ hybridization analysis of a subset of MM tissue sections seemed to indicate that the D9S171 locus may be involved in MM pathogenesis.
authors.affiliation: Istituto di Chimica Biomolecolare, CNR, Alghero, 07040 Santa Maria La Palma (Sassari), Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Casula
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Ascierto
authors.forename: Antonio
authors.initials: A
authors.lastname: Cossu
authors.forename: Maria C
authors.initials: MC
authors.lastname: Sini
authors.forename: Silvia
authors.initials: S
authors.lastname: Tore
authors.forename: Maria
authors.initials: M
authors.lastname: Colombino
authors.forename: Maria P
authors.initials: MP
authors.lastname: Satta
authors.forename: Antonella
authors.initials: A
authors.lastname: Manca
authors.forename: Carla
authors.initials: C
authors.lastname: Rozzo
authors.forename: Sabrina M
authors.initials: SM
authors.lastname: Satriano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castello
authors.forename: Amelia
authors.initials: A
authors.lastname: Lissia
authors.forename: Francesco
authors.initials: F
authors.lastname: Tanda
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
mesh_terms: D002899:Chromosomes, Human, Pair 9; D004252:DNA Mutational Analysis; D005091:Exons; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006239:Haplotypes; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D007558:Italy; D008297:Male; D008545:Melanoma / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA