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BRCA1 and BRCA2 Testing through Next Generation Sequencing in a Small Cohort of Italian Breast/Ovarian Cancer Patients: Novel Pathogenic and Unknown Clinical Significance Variants

1
Dipartimento Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, 00168 Rome, Italy
2
Ambulatorio Genetica Medica e Citogenetica Clinica, Poliambulatorio Sant’Anna, ASL Roma 1, Via Garigliano 55, 00198 Rome, Italy
3
Department Woman and Child Health Sciences, Catholic University of the Sacred Heart, 00168 Rome, Italy
4
Dipartimento di Medicina Molecolare e Biotecnologie Mediche Università Federico II, CEINGE Biotecnologie Avanzate, 80145 Naples, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(14), 3442; https://doi.org/10.3390/ijms20143442
Received: 6 May 2019 / Revised: 8 July 2019 / Accepted: 11 July 2019 / Published: 12 July 2019
(This article belongs to the Section Molecular Genetics and Genomics)
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Abstract

The aim of this report is to describe results of BRCA1 and BRCA2 Next Generation Sequencing Analysis (NGS) analysis in 132 selected Italian patients with breast/ovarian cancer. A NGS pipeline with a reliable Copy Number Variation (CNV) prediction algorithm was applied. In addition, VarSome and Priors V2.0 Software were employed for in silico analysis of novel missense variants. A total of 37 BRCA1 and BRCA2 pathogenic variants were found in 34 unrelated subjects with a frequency of positive patients of 25.7% (34/132). Twenty-four deleterious variants were detected in BRCA1 (representing the 64.9% of all identified pathogenic defects) and thirteen (35.1% of all identified pathogenic variants) in BRCA2 gene. The percentage of patients carrying a variant of unknown significance (VUS) was 7.5% (10/132). In addition, seven novel variants (five in BRCA2 and two in BRCA1 gene), never previously reported, were identified. Our approach represents a robust and easy-to-use method for full BRCA1/2 screening. However, a consistent number of our high-risk families still remained without a satisfying answer. Necessarily, further collective efforts must be directed to a definitive classification of VUSs. The future auspice is that the use of multi-gene panel and more advanced screenings, such as whole exome sequencing and/or RNA seq, in routine diagnostics increases the detection rate. View Full-Text
Keywords: molecular diagnosis; genetic testing; breast cancer; ovarian cancer; NGS; BRCA1/2 genes molecular diagnosis; genetic testing; breast cancer; ovarian cancer; NGS; BRCA1/2 genes
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Concolino, P.; Gelli, G.; Rizza, R.; Costella, A.; Scambia, G.; Capoluongo, E. BRCA1 and BRCA2 Testing through Next Generation Sequencing in a Small Cohort of Italian Breast/Ovarian Cancer Patients: Novel Pathogenic and Unknown Clinical Significance Variants. Int. J. Mol. Sci. 2019, 20, 3442.

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