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Open Access 01-12-2021 | Breast Cancer | Research article

Comprehensive analysis of germline mutations in northern Brazil: a panel of 16 genes for hereditary cancer-predisposing syndrome investigation

Authors: Amanda Ferreira Vidal, Rafaella Sousa Ferraz, Antonette El-Husny, Caio Santos Silva, Tatiana Vinasco-Sandoval, Leandro Magalhães, Milene Raiol-Moraes, Williams Fernandes Barra, Cynthia Lara Brito Lins Pereira, Paulo Pimentel de Assumpção, Leonardo Miranda de Brito, Ricardo Assunção Vialle, Sidney Santos, Ândrea Ribeiro-dos-Santos, André M. Ribeiro-dos-Santos

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

Next generation sequencing (NGS) has been a handy tool in clinical practice, mainly due to its efficiency and cost-effectiveness. It has been widely used in genetic diagnosis of several inherited diseases, and, in clinical oncology, it may enhance the discovery of new susceptibility genes and enable individualized care of cancer patients. In this context, we explored a pan-cancer panel in the investigation of germline variants in Brazilian patients presenting clinical criteria for hereditary cancer syndromes or familial history.

Methods

Seventy-one individuals diagnosed or with familial history of hereditary cancer syndromes were submitted to custom pan-cancer panel including 16 high and moderate penetrance genes previously associated with hereditary cancer syndromes (APC, BRCA1, BRCA2, CDH1, CDKN2A, CHEK2, MSH2, MSH6, MUTYH, PTEN, RB1, RET, TP53, VHL, XPA and XPC). All pathogenic variants were validated by Sanger sequencing.

Results

We identified a total of eight pathogenic variants among 12 of 71 individuals (16.9%). Among the mutation-positive subjects, 50% were diagnosed with breast cancer and had mutations in BRCA1, CDH1 and MUTYH. Notably, 33.3% were individuals diagnosed with polyposis or who had family cases and harbored pathogenic mutations in APC and MUTYH. The remaining individuals (16.7%) were gastric cancer patients with pathogenic variants in CDH1 and MSH2. Overall, 54 (76.05%) individuals presented at least one variant uncertain significance (VUS), totalizing 81 VUS. Of these, seven were predicted to have disease-causing potential.

Conclusion

Overall, analysis of all these genes in NGS-panel allowed the identification not only of pathogenic variants related to hereditary cancer syndromes but also of some VUS that need further clinical and molecular investigations. The results obtained in this study had a significant impact on patients and their relatives since it allowed genetic counselling and personalized management decisions.

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Title: Comprehensive analysis of germline mutations in northern Brazil: a panel of 16 genes for hereditary cancer-predisposing syndrome investigation
Authors: Amanda Ferreira Vidal
Rafaella Sousa Ferraz
Antonette El-Husny
Caio Santos Silva
Tatiana Vinasco-Sandoval
Leandro Magalhães
Milene Raiol-Moraes
Williams Fernandes Barra
Cynthia Lara Brito Lins Pereira
Paulo Pimentel de Assumpção
Leonardo Miranda de Brito
Ricardo Assunção Vialle
Sidney Santos
Ândrea Ribeiro-dos-Santos
André M. Ribeiro-dos-Santos
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Breast Cancer
Gastric Cancer
Breast Cancer
Gastric Cancer
Familial Adenomatous Polyposis
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08089-9

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