Fast Detection of a BRCA2 Large Genomic Duplication by Next Generation Sequencing as a Single Procedure: A Case Report
CEINGE-Biotecnologie Avanzate, via Gaetano Salvatore 486, 80145 Naples, Italy
Department of Movement Sciences and Wellness (DiSMEB), University of Naples Parthenope, via Medina 40, 80133 Naples, Italy
Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, via Sergio Pansini 5, 80131 Naples, Italy
Oncology Division, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy
Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy
IRCCS-Fondazione SDN, via Emanuele Gianturco 113, 80143 Naples, Italy
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2017, 18(11), 2487; https://doi.org/10.3390/ijms18112487
Received: 28 September 2017 / Revised: 6 November 2017 / Accepted: 18 November 2017 / Published: 22 November 2017
(This article belongs to the Section Biochemistry)
The aim of this study was to verify the reliability of a next generation sequencing (NGS)-based method as a strategy to detect all possible BRCA mutations, including large genomic rearrangements. Genomic DNA was obtained from a peripheral blood sample provided by a patient from Southern Italy with early onset breast cancer and a family history of diverse cancers. BRCA molecular analysis was performed by NGS, and sequence data were analyzed using two software packages. Comparative genomic hybridization (CGH) array was used as confirmatory method. A novel large duplication, involving exons 4–26, of BRCA2 was directly detected in the patient by NGS workflow including quantitative analysis of copy number variants. The duplication observed was also found by CGH array, thus confirming its extent. Large genomic rearrangements can affect the BRCA1/2 genes, and thus contribute to germline predisposition to familial breast and ovarian cancers. The frequency of these mutations could be underestimated because of technical limitations of several routinely used molecular analysis, while their evaluation should be included also in these molecular testing. The NGS-based strategy described herein is an effective procedure to screen for all kinds of BRCA mutations.