Germline PALB2 Mutation in High-Risk Chinese Breast and/or Ovarian Cancer Patients

Simple Summary Breast cancer is the most commonly diagnosed cancer in women globally. BRCA1 and BRCA2 mutations are most prevalent in hereditary breast cancer and are associated with increased risk of breast and ovarian cancer. The PALB2 (partner and localizer of BRCA2) mutation was found to be associated with an increased risk of breast cancer and one of the most common mutations, after BRCA1 and BRCA2, in non-BRCA1/2 breast cancer patients. The prevalence of the PALB2 mutation in breast cancer varies across different ethnic groups; hence, it is of intense interest to evaluate the cancer risk and clinical association of PALB2 mutation in Chinese breast and/or ovarian cancer patients. The prevalence of the PALB2 mutation in breast cancer varies across different ethnic groups; hence, it is of intense interest to evaluate the cancer risk and clinical association of the PALB2 mutation in Chinese breast and/or ovarian cancer patients. We performed sequencing with a 6-gene test panel (BRCA1, BRCA2, TP53, PTEN, PALB2, and CDH1) to identify the prevalence of the PALB2 germline mutation among 2631 patients with breast and/or ovarian cancer. In this cohort, 39 mutations were identified with 24 types of mutation variants, where the majority of the mutations were frame-shift mutations and resulted in early termination. We also identified seven novel PALB2 mutations. Most of the PALB2 mutation carriers had breast cancer (36, 92.3%) and were more likely to have family history of breast cancer (19, 48.7%). The majority of the breast tumors were invasive ductal carcinoma (NOS type) (34, 81.0%) and hormonal positive (ER: 32, 84.2%; PR: 23, 60.5%). Pathogenic mutations of PALB2 were found in 39 probands with a mutation frequency of 1.6% and 1% in breast cancer and ovarian cancer patients, respectively. PALB2 mutation carriers were more likely have hormonal positive tumors and were likely to have familial aggregation of breast cancer.