Spectrum and clinical relevance of PALB2 germline mutations in 7657 Chinese BRCA1/2-negative breast cancer patients

Abstract

To investigate the prevalence and clinical relevance of PALB2 germline mutations in BRCA1/2-negative breast cancer patients. The exons and intron–exon boundaries of the PALB2 gene were sequenced by multigene panel testing in a cohort of 7657 Chinese BRCA1/2-negative breast cancer patients. Of the 7657 patients, 54 (0.71%) carried pathogenic PALB2 germline mutations, all of which were nonsense or frameshift mutations leading to a truncated protein. The 54 patients carried 42 distinct pathogenic mutations, of which 17 (40.5%) were novel and 8 were recurrent mutations. Compared with non-carriers, PALB2 pathogenic mutation carriers developed breast cancer at a younger age (47.52 years vs. 51.35 years, p\u2009=\u20090.016) and were more likely to have triple-negative (24.1% vs. 13.4%, p\u2009=\u20090.022) or HER2 negative (87.0% vs. 74.2%, p\u2009=\u20090.031) breast cancer and large breast tumors (>\u20092 cm) at diagnosis (72.2% vs. 57.0%, p\u2009=\u20090.024). PALB2 mutation carriers were also more likely to have family histories of breast and/or ovarian cancer (27.8% vs. 8.4%, p\u2009<\u20090.001) and any types of cancer (57.4% vs. 31.6%, p\u2009<\u20090.001) when compared with non-carriers. PALB2 germline mutations are present at 0.71% in Chinese BRCA1/2-negative breast cancer patients and are more frequent in patients with triple-negative breast cancer and family histories of breast and/or ovarian cancer.