mutation analysis of brca1, brca2, palb2 and brd7 in a hospital-based series of german patients with triple-negative breast cancer突变分析brca1、brca2 palb2和brd7医院一系列德国三阴性乳腺癌患者.pdfVIP

Mutation Analysis of BRCA1, BRCA2, PALB2 and BRD7 in a Hospital-Based Series of German Patients with Triple- Negative Breast Cancer 1 1,2 ¨ 1 3 1 ¨ 4 Franziska Pern , Natalia Bogdanova , Peter Schurmann , Min Lin , Aysun Ay , Florian Langer , 1 2 1 ¨ 1 Peter Hillemanns , Hans Christiansen , Tjoung-Won Park-Simon , Thilo Dork * 1 Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany, 2 Clinics of Radiation Oncology, Hannover Medical School, Hannover, Germany, 3 Fluidigm Corporation, San Francisco, California, United States of America, 4 Institute of Pathology, Hannover Medical School, Hannover, Germany Abstract Triple-negative breast cancer (TNBC) is an aggressive form of breast carcinoma with a poor prognosis. Recent evidence suggests that some patients with TNBC harbour germ-line mutations in DNA repair genes which may render their tumours susceptible to novel therapies such as treatment with PARP inhibitors. In the present study, we have investigated a hospital- based series of 40 German patients with TNBC for the presence of germ-line mutations in BRCA1, BRCA2, PALB2, and BRD7 genes. Microfluidic array PCR and next-generation sequencing was used for BRCA1 and BRCA2 analysis while conventional high-resolution melting and Sanger sequencing was applied to study the coding regions of PALB2 and BRD7, respectively. Truncating mutations in BRCA1 were found in six patients, and truncating mutations in BRCA2 and PALB2 were detected in one patient each, whereas no truncating mutation was identified in BRD7. One patient was a double heterozygote for the PALB2 mutation, c.758insT,