• Kun Zhang, Jiaojiao Zhou, Xuan Zhu, Meng Luo, Chunjing Xu, JieKai Yu, Mei Deng, Shu Zheng, and Yiding Chen.
• Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jie-Fang Rd, Hangzhou, 310009, Zhejiang, China.
• Breast Cancer Res. Treat. 2017 Dec 1; 166 (3): 865-873.

BackgroundPALB2 (Partner and Localizer of BRCA2) is recently recognized as a breast cancer predisposition gene. Germline loss-of-function mutations in PALB2 lead to increased breast cancer risk. Since the germline mutation frequency of PALB2 is much less than BRCA1/2, the distinct mutation spectrum of PALB2 is still obscure. To verify the utility of PALB2 genetic testing in Chinese population, we assessed the mutational frequency, spectrum, and predictors of the PALB2 gene in a sequential series of Chinese breast cancer patients from our Research DNA Bank.MethodsWe examined breast cancer samples (n = 2279) collected from 2000 through 2016 from Chinese patients who agreed to participate in research DNA banking. To identify the mutations, complete coding sequence and intron-exon boundaries of PALB2 were screened with Next-Generation Sequencing. Personal and family histories were synchronously collected for mutation identification.ResultsAmong the 2279 breast cancer patients, 305 patients were familial breast cancer cases and the rest 1967 patients were sporadic breast cancer cases. PALB2 loss-of-function mutation carriers accounted for 1.31% (n = 4) and 0.56% (n = 11) in familial and sporadic breast cancer cohort separately. In total, 30 missenses, four nonsenses, three frameshifts, three splicings, and one inframe deletions of PALB2 were identified in this study. Among the deleterious mutations, PALB2 c.1744C>T, c.2748+1G>A, c.2749-1G>C, c.3114-1G>A were newly identified in sporadic breast cancer, and c.3271delC newly found in familial breast cancer. Based on in silico analysis, we found two potentially damaging missense variants with high frequency: c.1213C>G, c.3054G>C, and classified six new potentially damaging missense variants.ConclusionsOur data presented the germline mutation status of PALB2 in Chinese breast cancer patients, suggesting that loss-of-function germline mutations of PALB2 are important in both familial and sporadic breast cancer. Clinically, these data may be helpful in genetic counseling of breast cancer patients with PALB2 germline mutation.

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