title: CDKN2A mutation and deletion status in thin and thick primary melanoma.
abstract: Human melanoma cell lines and tumor tissue from familial and sporadic melanomas have frequent, nonrandom chromosomal breaks and deletions on chromosome 9p21, a region that includes the tumor suppressor gene CDKN2A/p16INK4A. Germ-line mutations within this gene have been observed in some familial melanoma kindreds, but somatic mutation in sporadic primary melanoma is infrequent. Thirty-nine archival, paraffin-embedded, sporadic, primary cutaneous malignant melanomas (20 >3-mm-thick and 19 <0.75-mm-thick cases) were examined for mutations of the CDKN2A gene using single-strand conformational polymorphism analysis and direct sequencing. No mutations were detected. Loss of heterozygosity for the 9p21 microsatellite marker D9S942 was detected in 6 of 17 informative thick lesions (35%) but 0 of 18 thin lesions (P = 0.006). These results support other studies indicating that intragenic mutation is an infrequent mechanism of CDKN2A inactivation in primary melanoma. The finding of loss of heterozygosity for the 9p21 microsatellite D9S942 in thick but not thin primary melanoma suggests that deletion or inactivation of CDKN2A or other tumor suppressor gene(s) at this locus is involved in the progression rather than initiation of sporadic malignant melanoma.
authors.affiliation: Department of Tissue and Cell Pathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, New South Wales, Australia.
authors.forename: A R
authors.initials: AR
authors.lastname: Cachia
authors.forename: J O
authors.initials: JO
authors.lastname: Indsto
authors.forename: K M
authors.initials: KM
authors.lastname: McLaren
authors.forename: G J
authors.initials: GJ
authors.lastname: Mann
authors.forename: M J
authors.initials: MJ
authors.lastname: Arends
mesh_terms: D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D019942:Genes, p16 / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*