The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype.
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.
Meijers-Heijboer
Hanne
H
Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
Wijnen
Juul
J
Vasen
Hans
H
Wasielewski
Marijke
M
Wagner
Anja
A
Hollestelle
Antoinette
A
Elstrodt
Fons
F
van den Bos
Renate
R
de Snoo
Anja
A
Fat
Grace Tjon A
GT
Brekelmans
Cecile
C
Jagmohan
Shantie
S
Franken
Patrick
P
Verkuijlen
Paul
P
van den Ouweland
Ans
A
Chapman
Pamela
P
Tops
Carli
C
Möslein
Gabriela
G
Burn
John
J
Lynch
Henry
H
Klijn
Jan
J
Fodde
Riccardo
R
Schutte
Mieke
M
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
D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases