Fast Detection of a BRCA2 Large Genomic Duplication by Next Generation Sequencing as a Single Procedure: A Case Report

• Published in: International journal of molecular sciences Vol. 18; no. 11; p. 2487
• Main Authors: Nunziato, Marcella, Starnone, Flavio, Lombardo, Barbara, Pensabene, Matilde, Condello, Caterina, Verdesca, Francesco, Carlomagno, Chiara, De Placido, Sabino, Pastore, Lucio, Salvatore, Francesco, D'Argenio, Valeria
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22-11-2017; MDPI
• Subjects: aCGH; Adult; BRCA1 protein; BRCA2; BRCA2 protein; Breast cancer; Case Report; Case reports; Comparative Genomic Hybridization; Computational Biology - methods; Copy number; Data processing; Deoxyribonucleic acid; DNA; Exons; Female; Gene Duplication; Gene Rearrangement; Genes, BRCA2; Genetic Predisposition to Disease; Genetic Testing; Genomics - methods; Germ-Line Mutation; Health risk assessment; Hereditary Breast and Ovarian Cancer Syndrome - diagnosis; Hereditary Breast and Ovarian Cancer Syndrome - genetics; hereditary breast cancer; High-Throughput Nucleotide Sequencing; Humans; Hybridization; large genomic rearrangements; Mutation; next generation sequencing; Ovarian cancer; Pedigree; Peripheral blood; Quantitative analysis; Reproduction (copying); Software packages; Workflow; large genomic rearrangements; hereditary breast cancer; BRCA2; next generation sequencing; aCGH
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18112487

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
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.
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
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
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
mutations.