title: Deletion of the MGMT gene in familial melanoma.
abstract: The DNA repair gene MGMT (O-6-methylguanine-DNA methyltransferase) is important for maintaining normal cell physiology and genomic stability. Alterations in MGMT play a critical role in the development of several types of cancer, including glioblastoma, lung cancer, and colorectal cancer. The purpose of this study was to explore the function of genetic alterations in MGMT and their connection with familial melanoma (FM). Using multiplex ligation-dependent probe amplification, we identified a deletion that included the MGMT gene in one of 64 families with a melanoma predisposition living in western Sweden. The mutation segregated with the disease as a heterozygous deletion in blood-derived DNA, but a homozygous deletion including the promoter region and exon 1 was seen in tumor tissue based on Affymetrix 500K and 6.0 arrays. By sequence analysis of the MGMT gene in the other 63 families with FM from western Sweden, we identified four common polymorphisms, nonfunctional, as predominantly described in previous studies. We conclude that inherited alterations in the MGMT gene might be a rare cause of FM, and we suggest that MGMT contributes to melanoma predisposition.
authors.affiliation: Department of Dermatology, Institute of Clinical Sciences, Sahlgrenska University Hospital, SE-413 45, Göteborg, Sweden.
authors.forename: Frida
authors.initials: F
authors.lastname: Appelqvist
authors.forename: Maria
authors.initials: M
authors.lastname: Yhr
authors.forename: Anna
authors.initials: A
authors.lastname: Erlandson
authors.forename: Tommy
authors.initials: T
authors.lastname: Martinsson
authors.forename: Charlotta
authors.initials: C
authors.lastname: Enerbäck
mesh_terms: D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005091:Exons; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012878:Skin Neoplasms / Q000235:genetics*; D013548:Sweden; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000096142:Cutaneous Malignant Melanoma
chemical_list: D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes