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Comprehensive sequencing of PALB2 in patients with breast cancer suggests PALB2 mutations explain a subset of hereditary breast cancer
Author(s) -
Fernandes Priscilla H.,
Saam Jennifer,
Peterson Jenny,
Hughes Elisha,
Kaldate Rajesh,
Cummings Shelly,
Theisen Aaron,
Chen Sonia,
Trost Jeffrey,
Roa Benjamin B.
Publication year - 2014
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.28504
Subject(s) - palb2 , medicine , breast cancer , cancer , mutation , oncology , genetics , germline mutation , gene , biology
BACKGROUND This study sought to determine the prevalence of PALB2 mutations in a cohort referred for diagnostic testing for hereditary breast cancer. METHODS Sanger sequencing was used to analyze the entire coding region and flanking introns of PALB2 in anonymized DNA samples from 1479 patients. Samples were stratified into a “high‐risk” group, 955 samples from individuals predicted to have a high probability of carrying a mutation in BRCA1 or BRCA2 based on their personal and family history, and a “lower‐risk” group consisting of 524 samples from patients with breast cancer, but fewer risk factors for being a BRCA1 or BRCA2 mutation carrier. All patients were known to be negative for deleterious sequence mutations and large rearrangements in BRCA1 and BRCA2 . RESULTS We identified 12 disease‐associated PALB2 mutations among the 1479 patients (0.8%). The PALB2 mutations included 8 nonsense, 3 frameshift mutations and a splice‐site mutation. The mutation prevalence for the high‐risk population was 1.05% (95% CI = 0.5‐1.92), whereas that for the lower‐risk population was 0.38% (95% CI = 0.05‐1.37). We identified 59 PALB2 variants of uncertain significance (VUS) among 57 of the 1479 patients (3.9%). CONCLUSIONS These results suggest that PALB2 mutations occur at a frequency of ∼1% in patients with hereditary breast cancer. Cancer 2014;120:963–967 . © 2013 American Cancer Society .