title: Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome.
abstract: The hCHK2 gene encodes the human homolog of the yeast Cds1 and Rad53 G2 checkpoint kinases, whose activation in response to DNA damage prevents cellular entry into mitosis. Here, it is shown that heterozygous germ line mutations in hCHK2 occur in Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in the TP53 gene. These observations suggest that hCHK2 is a tumor suppressor gene conferring predisposition to sarcoma, breast cancer, and brain tumors, and they also provide a link between the central role of p53 inactivation in human cancer and the well-defined G2 checkpoint in yeast.
authors.affiliation: Massachusetts General Hospital Center for Cancer Risk Analysis and Harvard Medical School, Building 149, Charlestown, MA 02129, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Bell
authors.forename: J M
authors.initials: JM
authors.lastname: Varley
authors.forename: T E
authors.initials: TE
authors.lastname: Szydlo
authors.forename: D H
authors.initials: DH
authors.lastname: Kang
authors.forename: D C
authors.initials: DC
authors.lastname: Wahrer
authors.forename: K E
authors.initials: KE
authors.lastname: Shannon
authors.forename: M
authors.initials: M
authors.lastname: Lubratovich
authors.forename: S J
authors.initials: SJ
authors.lastname: Verselis
authors.forename: K J
authors.initials: KJ
authors.lastname: Isselbacher
authors.forename: J F
authors.initials: JF
authors.lastname: Fraumeni
authors.forename: J M
authors.initials: JM
authors.lastname: Birch
authors.forename: F P
authors.initials: FP
authors.lastname: Li
authors.forename: J E
authors.initials: JE
authors.lastname: Garber
authors.forename: D A
authors.initials: DA
authors.lastname: Haber
mesh_terms: D000483:Alleles; D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D005260:Female; D016193:G1 Phase; D016195:G2 Phase; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012509:Sarcoma / Q000235:genetics; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases