Supplementary Material for: 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 <i>MUTYH</i>, <i>BRCA2</i>, and <i>CHEK2</i> genes. Nine novel pathogenic/likely pathogenic variants were identified in <i>BRCA1</i>, <i>BRCA2</i>, <i>GALNT12</i>, <i>ATM</i>, <i>MLH1</i>, <i>MSH2</i>, <i>APC</i>, and <i>KIT</i> 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.

遗传性癌症综合征是指由癌症相关基因的生殖系突变（germline mutation）所引发的癌症遗传易感性。明确致病变异对于癌症家系中的患者及高危亲属均具有重要意义，因其可为临床治疗与继发性癌症预防提供关键指导依据。本研究对外周血样本采用Illumina MiSeq下一代测序（Next-Generation Sequencing, NGS）平台，实施了涵盖癌症相关基因的遗传性癌症检测panel检测。测序所得数据文件被导入至云端数据分析流程中进行处理。可报告变异参照美国医学遗传学与基因组学学会（American College of Medical Genetics and Genomics, ACMG）指南进行分类判定。本研究共纳入305名受试者，其中75名受试者被检出携带不同类型的致病性/疑似致病性变异。上述变异中，多数位于MUTYH、BRCA2及CHEK2基因内。研究人员在BRCA1、BRCA2、GALNT12、ATM、MLH1、MSH2、APC及KIT基因中，共鉴定出9种全新的致病性/疑似致病性变异。本研究获得了若干与遗传性癌症相关的新颖且具有临床研究价值的变异，同时证实下一代测序技术是癌症家系遗传风险评估中不可或缺的核心检测手段。