Simultaneous detection of genetic and copy number alterations in BRCA1/2 genes

// Yosuke Hirotsu 1 , Yoshihiko Ooka 1, 2 , Ikuko Sakamoto 3 , Hiroshi Nakagomi 4 and Masao Omata 1, 5 1 Genome Analysis Center, Yamanashi Central Hospital, Kofu, Yamanashi 400-8506, Japan 2 Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8677, Japan 3 Department of Obstetrics and Gynecology, Yamanashi Central Hospital, Fujimi Kofu-City, Yamanashi 400-8506, Japan 4 Department of Breast Surgery, Yamanashi Central Hospital, Yamanashi 400-8506, Japan 5 University of Tokyo, Hongo, Bunkyo-Ku, Tokyo 113-8655, Japan Correspondence to: Yosuke Hirotsu, email: hirotsu-bdyu@ych.pref.yamanashi.jp Keywords: BRCA1; BRCA2; mutation; copy number; diagnosis Received: August 09, 2017      Accepted: November 11, 2017      Published: December 06, 2017 ABSTRACT Germline mutations in BRCA1 and BRCA2 genes ( BRCA1/2 ) predispose to hereditary breast and ovarian cancer syndrome (HBOC), and their dysregulation increases the risk of cancers. The detection of pathogenic BRCA1/2 variants is essential for the diagnosis and prevention of HBOC, and for offering treatment decisions for patients. Therefore, there is a growing demand for the development of accurate, rapid assay systems that simultaneously detect pathogenic variants and copy number alterations. Here, we tested Thermo Fisher Scientific’s newly developed Oncomine ® BRCA1/2 Panel. We showed that all mutations in standard reference DNA were detected with high accuracy, and that values of allelic fractions were detected with high concordance ( R 2 = 0.9986). The Oncomine ® BRCA1/2 Panel detected 21 pathogenic germline variants in 147 patients with breast and/or ovarian cancer, of which 20 were detected by the previously-launched Ion AmpliSeq™ BRCA1/2 Panel, except for one frameshift mutation. The Oncomine ® BRCA1/2 Panel precisely captured one additional frameshift mutation, which is difficult to detect because of the homopolymer site. Large genomic deletion was identified in one sample, which was previously detected by multiplex ligation-dependent probe amplification. Oncomine ® BRCA1/2 Panel could accurately detect pathogenic variant and copy number alteration, and be an alternative assay to investigate BRCA1/2 germline and somatic mutations.