title: p53, CHK2, and CHK1 genes in Finnish families with Li-Fraumeni syndrome: further evidence of CHK2 in inherited cancer predisposition.
abstract: Germ-line mutations in the p53 gene predispose individuals to Li-Fraumeni syndrome (LFS). The cell cycle checkpoint kinases CHK1 and CHK2 act upstream of p53 in DNA damage responses, and recently rare germ-line mutations in CHK2 were reported in LFS families. We have analyzed CHK1, CHK2, and p53 genes for mutations in 44 Finnish families with LFS, Li-Fraumeni-like syndrome, or families phenotypically suggestive of LFS with conformation-sensitive gel electrophoresis. Five different disease-causing mutations were observed in 7 families (7 of 44 families; 15.9%): 4 in the p53 gene (5 of 44 families; 11.4%) and 1 in the CHK2 gene (2 of 44 families; 4.5%). Interestingly, the other CHK2-mutation carrier also has a mutation in the MSH6 gene. The cancer phenotype in the CHK2-families was not characteristic of LFS, and may indicate variable phenotypic expression in the rare families with CHK2 mutations. No mutations in the CHK1 gene were identified. Additional work is necessary to completely unravel the molecular background of LFS.
authors.affiliation: Department of Obstetrics and Gynecology, Helsinki University Central Hospital, FIN-00029 Helsinki, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Vahteristo
authors.forename: A
authors.initials: A
authors.lastname: Tamminen
authors.forename: P
authors.initials: P
authors.lastname: Karvinen
authors.forename: H
authors.initials: H
authors.lastname: Eerola
authors.forename: C
authors.initials: C
authors.lastname: Eklund
authors.forename: L A
authors.initials: LA
authors.lastname: Aaltonen
authors.forename: C
authors.initials: C
authors.lastname: Blomqvist
authors.forename: K
authors.initials: K
authors.lastname: Aittomäki
authors.forename: H
authors.initials: H
authors.lastname: Nevanlinna
mesh_terms: D000328:Adult; D000368:Aged; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D008297:Male; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D010375:Pedigree; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases
chemical_list: D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases