Comprehensive analysis of germline mutations in northern Brazil: a panel of 16 genes for hereditary cancer-predisposing syndrome investigation
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 susceptibil...
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2021-04-01
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Online Access: | https://doi.org/10.1186/s12885-021-08089-9 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Comprehensive analysis of germline mutations in northern Brazil: a panel of 16 genes for hereditary cancer-predisposing syndrome investigation BMC Cancer Hereditary cancer Next generation sequencing Pan-cancer panel Pathogenic variant |
author_facet |
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 |
author_sort |
Amanda Ferreira Vidal |
title |
Comprehensive analysis of germline mutations in northern Brazil: a panel of 16 genes for hereditary cancer-predisposing syndrome investigation |
title_short |
Comprehensive analysis of germline mutations in northern Brazil: a panel of 16 genes for hereditary cancer-predisposing syndrome investigation |
title_full |
Comprehensive analysis of germline mutations in northern Brazil: a panel of 16 genes for hereditary cancer-predisposing syndrome investigation |
title_fullStr |
Comprehensive analysis of germline mutations in northern Brazil: a panel of 16 genes for hereditary cancer-predisposing syndrome investigation |
title_full_unstemmed |
Comprehensive analysis of germline mutations in northern Brazil: a panel of 16 genes for hereditary cancer-predisposing syndrome investigation |
title_sort |
comprehensive analysis of germline mutations in northern brazil: a panel of 16 genes for hereditary cancer-predisposing syndrome investigation |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2021-04-01 |
description |
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. |
topic |
Hereditary cancer Next generation sequencing Pan-cancer panel Pathogenic variant |
url |
https://doi.org/10.1186/s12885-021-08089-9 |
work_keys_str_mv |
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doaj-8f815626122642838232d85a9b8cb17a2021-04-11T11:42:24ZengBMCBMC Cancer1471-24072021-04-012111810.1186/s12885-021-08089-9Comprehensive analysis of germline mutations in northern Brazil: a panel of 16 genes for hereditary cancer-predisposing syndrome investigationAmanda Ferreira Vidal0Rafaella Sousa Ferraz1Antonette El-Husny2Caio Santos Silva3Tatiana Vinasco-Sandoval4Leandro Magalhães5Milene Raiol-Moraes6Williams Fernandes Barra7Cynthia Lara Brito Lins Pereira8Paulo Pimentel de Assumpção9Leonardo Miranda de Brito10Ricardo Assunção Vialle11Sidney Santos12Ândrea Ribeiro-dos-Santos13André M. Ribeiro-dos-Santos14Laboratory of Human and Medical Genetics, Graduate Program Genetics and Molecular Biology, Federal University of ParáLaboratory of Human and Medical Genetics, Graduate Program Genetics and Molecular Biology, Federal University of ParáBettina Ferro de Souza University Hospital, Federal University of ParáLaboratory of Human and Medical Genetics, Graduate Program Genetics and Molecular Biology, Federal University of ParáLaboratory of Human and Medical Genetics, Graduate Program Genetics and Molecular Biology, Federal University of ParáLaboratory of Human and Medical Genetics, Graduate Program Genetics and Molecular Biology, Federal University of ParáLaboratory of Human and Medical Genetics, Graduate Program Genetics and Molecular Biology, Federal University of ParáJoão de Barros Barreto University Hospital, Federal University of ParáJoão de Barros Barreto University Hospital, Federal University of ParáCenter of Oncology Research, Federal University of ParáLaboratory of Human and Medical Genetics, Graduate Program Genetics and Molecular Biology, Federal University of ParáLaboratory of Human and Medical Genetics, Graduate Program Genetics and Molecular Biology, Federal University of ParáLaboratory of Human and Medical Genetics, Graduate Program Genetics and Molecular Biology, Federal University of ParáLaboratory of Human and Medical Genetics, Graduate Program Genetics and Molecular Biology, Federal University of ParáLaboratory of Human and Medical Genetics, Graduate Program Genetics and Molecular Biology, Federal University of ParáAbstract 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.https://doi.org/10.1186/s12885-021-08089-9Hereditary cancerNext generation sequencingPan-cancer panelPathogenic variant |