Carrier Detection in a Normal Individual for 69 Genes Involved in Familial Cancer Syndromes Using Whole Exome Sequencing

Cancer, with a high rate of mortalities worldwide, pose a major threat to human health. Although family history accounts for at least 5-10% of all cancers, it is conferred to be as a significant risk of developing cancer. Recently, application of high speed and low cost high-throughput nucleotide sequencing technologies has provided an opportunity to assess cancer risk in at risk healthy individuals. The present study has aimed to detect susceptible variants relevant to 69 known cancer genes on a 42-year-old Iranian healthy volunteer with familial history of cancer syndromes using Whole Exome Sequencing (WES). Exome enrichment and sequencing were applied using SureSelect V4 kit and Illumina Hiseq2000, respectively. Analysis of data was carried out by Insilico thoroughly methods. Some filtering criteria were considered to exclude the common (MAF>1%) and nonfunctional variants as well as any variants out of +- 2 bp exons boundaries according to RefSeq database. We focused on deleterious rare alternations. To further validation, data was compared to 300 Iranian normal controls and confirmed by Sanger sequencing method. As a result, 89 variants were identified totally which passed filtering process and eventually, the data emerging from Insilico analysis revealed a novel variant of WRN gene (c.953_954delTTA). Given the fact that cancer potentially could be predictable, genetic screening of hereditable deleterious variants in at risk individuals is crucial stage stag in terms of improving the quality of life allowing prevention and control. In this regards, WES, as cost-benefit diagnostic tool, effectively is capable of determining all susceptibility cancer genes variations predisposing to disease. The project as a first carrier detection is being emerged as a new insight to take a step to establish new genetic molecular approach in our country, as well as supporting the potential utilization of powerful WES in the field of early detection.