title: Allelic losses on chromosome arm 10q and mutation of the PTEN (MMAC1) tumour suppressor gene in primary and metastatic malignant melanomas.
abstract: Malignant melanomas frequently show loss of alleles on the long arm of chromosome 10. The PTEN (MMAC1) gene has been identified as a tumour suppressor gene at 10q23.3 that is mutated in various types of advanced human cancers. We have investigated a series of 40 sporadic melanomas from 37 patients (15 primary cutaneous melanomas and 25 melanoma metastases) for allelic losses on chromosome 10, as well as for deletion and mutation of the PTEN gene. Microsatellite analysis revealed loss of heterozygosity at loci located on 10q in tumours from 15 of 34 patients investigated (44%). Somatic PTEN mutations were identified in melanomas from 4 of 37 patients (11%), all of whom had metastatic disease. In two of these patients, the tumours had additionally lost one PTEN allele, indicating complete loss of wild-type PTEN in the tumour cells. Our findings corroborate that loss of heterozygosity on chromosome 10 is a frequent aberration in malignant melanomas and implicate PTEN as a tumour suppressor gene inactivated by somatic mutation in a fraction of these tumours.
authors.affiliation: Department of Dermatology, Heinrich-Heine University, Düsseldorf, Germany. g.reifenberger@uni-bonn.de
authors.forename: J
authors.initials: J
authors.lastname: Reifenberger
authors.forename: M
authors.initials: M
authors.lastname: Wolter
authors.forename: J
authors.initials: J
authors.lastname: Boström
authors.forename: R
authors.initials: R
authors.lastname: Büschges
authors.forename: K W
authors.initials: KW
authors.lastname: Schulte
authors.forename: M
authors.initials: M
authors.lastname: Megahed
authors.forename: T
authors.initials: T
authors.lastname: Ruzicka
authors.forename: G
authors.initials: G
authors.lastname: Reifenberger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000556:secondary; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D025521:Tumor Suppressor Proteins
chemical_list: D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human