Identification of deleterious germline CHEK2 mutations and their association with breast and ovarian cancer.
Adult
Aged
Aged, 80 and over
Breast Neoplasms
/ genetics
Breast Neoplasms, Male
/ genetics
Case-Control Studies
Cell Line
Checkpoint Kinase 2
/ genetics
Czech Republic
Female
Gene Knockout Techniques
Genetic Predisposition to Disease
Germ-Line Mutation
Humans
Male
Middle Aged
Mutation, Missense
Ovarian Neoplasms
/ genetics
Sequence Deletion
Young Adult
CHEK2
KAP1
VUS
breast cancer
functional assay
germline mutations
ovarian cancer
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 10 2019
01 10 2019
Historique:
received:
06
02
2019
accepted:
24
04
2019
pubmed:
6
5
2019
medline:
18
1
2020
entrez:
4
5
2019
Statut:
ppublish
Résumé
Germline mutations in checkpoint kinase 2 (CHEK2), a multiple cancer-predisposing gene, increase breast cancer (BC) risk; however, risk estimates differ substantially in published studies. We analyzed germline CHEK2 variants in 1,928 high-risk Czech breast/ovarian cancer (BC/OC) patients and 3,360 population-matched controls (PMCs). For a functional classification of VUS, we developed a complementation assay in human nontransformed RPE1-CHEK2-knockout cells quantifying CHK2-specific phosphorylation of endogenous protein KAP1. We identified 10 truncations in 46 (2.39%) patients and in 11 (0.33%) PMC (p = 1.1 × 10
Substances chimiques
Checkpoint Kinase 2
EC 2.7.1.11
CHEK2 protein, human
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1782-1797Informations de copyright
© 2019 UICC.