Genetic Characterization of Hereditary Cancer Syndromes Based on Targeted Next-Generation Sequencing

A hereditary cancer syndrome is a genetic predisposition to cancer caused by a germline mutation in cancer-related genes. Identifying the disease-causing variant is important for both the patient and relatives at risk in cancer families because this could be a guide in treatment and secondary cancer prevention. In this study, hereditary cancer panel harboring cancer-related genes was performed on MiSeq Illumina NGS system from peripheral blood samples. Sequencing files were fed into a cloud-based data analysis pipeline. Reportable variants were classified according to the American College of Medical Genetics and Genomics guidelines. Three hundred five individuals were included in the study. Different pathogenic/likely pathogenic variants were detected in 75 individuals. The majority of these variants were in the MUTYH, BRCA2, and CHEK2 genes. Nine novel pathogenic/likely pathogenic variants were identified in BRCA1, BRCA2, GALNT12, ATM, MLH1, MSH2, APC, and KIT genes. We obtained interesting and novel variants which could be related to hereditary cancer, and this study confirmed that NGS is an indispensable method for the risk assessment in cancer families.

Automated summary

In this study, novel pathogenic/likely pathogenic variants were identified in genes such as BRCA1, BRCA2, GALNT12, ATM, MLH1, MSH2, APC, and KIT, confirming the importance of NGS for risk assessment in cancer families. The majority of detected variants were found in the MUTYH, BRCA2, and CHEK2 genes. This study highlights the value of identifying disease-causing variants for treatment and prevention in hereditary cancer syndromes.