title: Germline CDKN2A mutation implicated in predisposition to multiple myeloma.
abstract: Germline mutations of the CDKN2A (p16(INK4A)) tumor suppressor gene predispose patients to melanoma and pancreatic carcinoma. In contrast, mutations of the murine CDKN2A gene predispose BALB/c mice to pristane-induced plasmacytoma. We describe here a family in which a germline mutation of CDKN2A is present in 4 individuals who developed melanoma as well as in a fifth family member who is suffering from multiple myeloma. To determine whether the CDKN2A mutation predisposed the myeloma patient to her disease, we carried out loss of heterozygosity studies on sorted bone marrow from this individual and observed loss of the wild type CDKN2A allele in the malignant plasma cells. We suggest that germline mutations of CDKN2A may predispose individuals to a wider variety of malignancy than has been hitherto reported, but that the expression of these cancers may depend heavily on the genetic background of the patient. (Blood. 2000;95:1869-1871)
authors.affiliation: Departments of Medical Biophysics, Clinical Science, and Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Dilworth
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: A K
authors.initials: AK
authors.lastname: Stewart
authors.forename: J R
authors.initials: JR
authors.lastname: Berenson
authors.forename: N
authors.initials: N
authors.lastname: Lassam
authors.forename: D
authors.initials: D
authors.lastname: Hogg
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000502:physiology*; D005091:Exons; D005260:Female; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008545:Melanoma / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000235:genetics*; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics*; D010375:Pedigree; D013045:Species Specificity
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16