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Frequency of mutations in individuals with breast cancer referred for BRCA 1 and BRCA 2 testing using next‐generation sequencing with a 25‐gene panel
Author(s) -
Tung Nadine,
Battelli Chiara,
Allen Brian,
Kaldate Rajesh,
Bhatnagar Satish,
Bowles Karla,
Timms Kirsten,
Garber Judy E.,
Herold Christina,
Ellisen Leif,
Krejdovsky Jill,
DeLeonardis Kim,
Sedgwick Kristin,
Soltis Kathleen,
Roa Benjamin,
Wenstrup Richard J.,
Hartman AnneRenee
Publication year - 2015
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.29010
Subject(s) - chek2 , palb2 , breast cancer , medicine , ovarian cancer , germline mutation , genetic testing , brca mutation , mutation , family history , cancer , oncology , genetics , gene , biology
BACKGROUND Next‐generation sequencing (NGS) allows for simultaneous sequencing of multiple cancer susceptibility genes and, for an individual, may be more efficient and less expensive than sequential testing. The authors assessed the frequency of deleterious germline mutations among individuals with breast cancer who were referred for BRCA1 and BRCA2 ( BRCA1/2 ) gene testing using a panel of 25 genes associated with inherited cancer predisposition. METHODS This was a cross‐sectional study using NGS in 2158 individuals, including 1781 who were referred for commercial BRCA1/2 gene testing (cohort 1) and 377 who had detailed personal and family history and had previously tested negative for BRCA1/2 mutations (cohort 2). RESULTS Mutations were identified in 16 genes, most frequently in BRCA1 , BRCA2 , CHEK2 , ATM , and PALB2 . Among the participants in cohort 1, 9.3% carried a BRCA1/2 mutation, 3.9% carried a mutation in another breast/ovarian cancer susceptibility gene, and 0.3% carried an incidental mutation in another cancer susceptibility gene unrelated to breast or ovarian cancer. In cohort 2, the frequency of mutations in breast/ovarian‐associated genes other than BRCA1/2 was 2.9%, and an additional 0.8% had an incidental mutation. In cohort 1, Lynch syndrome‐related mutations were identified in 7 individuals. In contrast to BRCA1/2 mutations, neither age at breast cancer diagnosis nor family history of ovarian or young breast cancer predicted for other mutations. The frequency of mutations in genes other than BRCA1/2 was lower in Ashkenazi Jews compared with non‐Ashkenazi individuals ( P =.026). CONCLUSIONS Using an NGS 25‐gene panel, the frequency of mutations in genes other than BRCA1/2 was 4.3%, and most mutations (3.9%) were identified in genes associated with breast/ovarian cancer. Cancer 2015;121:25–33 . © 2014 American Cancer Society .