title: Mutation analysis of the CHK2 gene in breast carcinoma and other cancers.
abstract: BACKGROUND
  Mutations in the CHK2 gene at chromosome 22q12.1 have been reported in families with Li-Fraumeni syndrome. Chk2 is an effector kinase that is activated in response to DNA damage and is involved in cell-cycle pathways and p53 pathways.
  
  
  METHODS
  We screened 139 breast tumors for loss of heterozygosity at chromosome 22q, using seven microsatellite markers, and screened 119 breast tumors with single-strand conformation polymorphism and DNA sequencing for mutations in the CHK2 gene.
  
  
  RESULTS
  Seventy-four of 139 sporadic breast tumors (53%) show loss of heterozygosity with at least one marker. These samples and 45 tumors from individuals carrying the BRCA2 999del5 mutation were screened for mutations in the CHK2 gene. In addition to putative polymorphic regions in short mononucleotide repeats in a non-coding exon and intron 2, a germ line variant (T59K) in the first coding exon was detected. On screening 1172 cancer patients for the T59K sequence variant, it was detected in a total of four breast-cancer patients, two colon-cancer patients, one stomach-cancer patient and one ovary-cancer patient, but not in 452 healthy individuals. A tumor-specific 5' splice site mutation at site +3 in intron 8 (TTgt [a --> c]atg) was also detected.
  
  
  CONCLUSIONS
  We conclude that somatic CHK2 mutations are rare in breast cancer, but our results suggest a tumor suppressor function for CHK2 in a small proportion of breast tumors. Furthermore, our results suggest that the T59K CHK2 sequence variant is a low-penetrance allele with respect to tumor growth.
authors.affiliation: Institute for Experimental Pathology, University of Iceland, Reykjavik, Iceland. siguring@hi.is
authors.forename: Sigurdur
authors.initials: S
authors.lastname: Ingvarsson
authors.forename: Bjarnveig I
authors.initials: BI
authors.lastname: Sigbjornsdottir
authors.forename: Chen
authors.initials: C
authors.lastname: Huiping
authors.forename: Sigridur H
authors.initials: SH
authors.lastname: Hafsteinsdottir
authors.forename: Gisli
authors.initials: G
authors.lastname: Ragnarsson
authors.forename: Rosa B
authors.initials: RB
authors.lastname: Barkardottir
authors.forename: Adalgeir
authors.initials: A
authors.lastname: Arason
authors.forename: Valgardur
authors.initials: V
authors.lastname: Egilsson
authors.forename: Jon T H
authors.initials: JT
authors.lastname: Bergthorsson
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D064447:Checkpoint Kinase 2; D002892:Chromosomes, Human, Pair 22; D003110:Colonic Neoplasms / Q000235:genetics; D005260:Female; D024522:Genes, BRCA2; D006579:Heterozygote; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D013274:Stomach Neoplasms / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics
chemical_list: D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases