title: The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype.
abstract: Because of genetic heterogeneity, the identification of breast cancer-susceptibility genes has proven to be exceedingly difficult. Here, we define a new subset of families with breast cancer characterized by the presence of colorectal cancer cases. The 1100delC variant of the cell cycle checkpoint kinase CHEK2 gene was present in 18% of 55 families with hereditary breast and colorectal cancer (HBCC) as compared with 4% of 380 families with non-HBCC (P<.001), thus providing genetic evidence for the HBCC phenotype. The CHEK2 1100delC mutation was, however, not the major predisposing factor for the HBCC phenotype but appeared to act in synergy with another, as-yet-unknown susceptibility gene(s). The unequivocal definition of the HBCC phenotype opens new avenues to search for this putative HBCC-susceptibility gene.
authors.affiliation: Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Hanne
authors.initials: H
authors.lastname: Meijers-Heijboer
authors.forename: Juul
authors.initials: J
authors.lastname: Wijnen
authors.forename: Hans
authors.initials: H
authors.lastname: Vasen
authors.forename: Marijke
authors.initials: M
authors.lastname: Wasielewski
authors.forename: Anja
authors.initials: A
authors.lastname: Wagner
authors.forename: Antoinette
authors.initials: A
authors.lastname: Hollestelle
authors.forename: Fons
authors.initials: F
authors.lastname: Elstrodt
authors.forename: Renate
authors.initials: R
authors.lastname: van den Bos
authors.forename: Anja
authors.initials: A
authors.lastname: de Snoo
authors.forename: Grace Tjon A
authors.initials: GT
authors.lastname: Fat
authors.forename: Cecile
authors.initials: C
authors.lastname: Brekelmans
authors.forename: Shantie
authors.initials: S
authors.lastname: Jagmohan
authors.forename: Patrick
authors.initials: P
authors.lastname: Franken
authors.forename: Paul
authors.initials: P
authors.lastname: Verkuijlen
authors.forename: Ans
authors.initials: A
authors.lastname: van den Ouweland
authors.forename: Pamela
authors.initials: P
authors.lastname: Chapman
authors.forename: Carli
authors.initials: C
authors.lastname: Tops
authors.forename: Gabriela
authors.initials: G
authors.lastname: Möslein
authors.forename: John
authors.initials: J
authors.lastname: Burn
authors.forename: Henry
authors.initials: H
authors.lastname: Lynch
authors.forename: Jan
authors.initials: J
authors.lastname: Klijn
authors.forename: Riccardo
authors.initials: R
authors.lastname: Fodde
authors.forename: Mieke
authors.initials: M
authors.lastname: Schutte
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D064447:Checkpoint Kinase 2; D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005787:Gene Frequency; D018816:Genes, cdc; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases
chemical_list: D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases