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

BMC Cancer

Antonette El-Husny¹  Paulo Pimentel de Assumpção²  Cynthia Lara Brito Lins Pereira³  Williams Fernandes Barra³  Rafaella Sousa Ferraz⁴  André M. Ribeiro-dos-Santos⁴  Milene Raiol-Moraes⁴  Amanda Ferreira Vidal⁴  Leonardo Miranda de Brito⁴  Caio Santos Silva⁴  Tatiana Vinasco-Sandoval⁴  Leandro Magalhães⁴  Ricardo Assunção Vialle⁴  Sidney Santos⁵  Ândrea Ribeiro-dos-Santos⁵ 

[1] Bettina Ferro de Souza University Hospital, Federal University of Pará, Belém, Pará, Brazil;Center of Oncology Research, Federal University of Pará, Belém, Pará, Brazil;João de Barros Barreto University Hospital, Federal University of Pará, Belém, Pará, Brazil;Center of Oncology Research, Federal University of Pará, Belém, Pará, Brazil;Laboratory of Human and Medical Genetics, Graduate Program Genetics and Molecular Biology, Federal University of Pará, Belém, Pará, Brazil;Laboratory of Human and Medical Genetics, Graduate Program Genetics and Molecular Biology, Federal University of Pará, Belém, Pará, Brazil;Center of Oncology Research, Federal University of Pará, Belém, Pará, Brazil;

关键词: Hereditary cancer;    Next generation sequencing;    Pan-cancer panel;    Pathogenic variant;   

DOI  :  10.1186/s12885-021-08089-9

来源: Springer

【 摘 要 】

BackgroundNext 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.MethodsSeventy-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.ResultsWe 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.ConclusionOverall, 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.

【 授权许可】

CC BY