scholarly journals 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

2019 ◽  
Vol 20 (14) ◽  
pp. 3442 ◽  
Author(s):  
Paola Concolino ◽  
Gianfranco Gelli ◽  
Roberta Rizza ◽  
Alessandra Costella ◽  
Giovanni Scambia ◽  
...  

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.

2020 ◽  
Vol 9 (1) ◽  
pp. 1
Author(s):  
Veronica Zelli ◽  
Chiara Compagnoni ◽  
Katia Cannita ◽  
Roberta Capelli ◽  
Carlo Capalbo ◽  
...  

Next generation sequencing (NGS) provides a powerful tool in the field of medical genetics, allowing one to perform multi-gene analysis and to sequence entire exomes (WES), transcriptomes or genomes (WGS). The generated high-throughput data are particularly suitable for enhancing the understanding of the genetic bases of complex, multi-gene diseases, such as cancer. Among the various types of tumors, those with a familial predisposition are of great interest for the isolation of novel genes or gene variants, detectable at the germline level and involved in cancer pathogenesis. The identification of novel genetic factors would have great translational value, helping clinicians in defining risk and prevention strategies. In this regard, it is known that the majority of breast/ovarian cases with familial predisposition, lacking variants in the highly penetrant BRCA1 and BRCA2 genes (non-BRCA), remains unexplained, although several less penetrant genes (e.g., ATM, PALB2) have been identified. In this scenario, NGS technologies offer a powerful tool for the discovery of novel factors involved in familial breast/ovarian cancer. In this review, we summarize and discuss the state of the art applications of NGS gene panels, WES and WGS in the context of familial breast/ovarian cancer.


2016 ◽  
Vol 5 (7) ◽  
pp. 1640-1646 ◽  
Author(s):  
Magdalena Koczkowska ◽  
Monika Zuk ◽  
Adam Gorczynski ◽  
Magdalena Ratajska ◽  
Marzena Lewandowska ◽  
...  

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Omar Alejandro Zayas-Villanueva ◽  
Luis Daniel Campos-Acevedo ◽  
José de Jesús Lugo-Trampe ◽  
David Hernández-Barajas ◽  
Juan Francisco González-Guerrero ◽  
...  

2016 ◽  
Vol 12 (2) ◽  
pp. 1192-1196 ◽  
Author(s):  
Farah Jouali ◽  
Fatima-Zahra Laarabi ◽  
Nabila Marchoudi ◽  
Ilham Ratbi ◽  
Siham Chafai Elalaoui ◽  
...  

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