Whole-Exome Sequencing Identified Damaging Rare/Germline Mutation in Familial Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) has been considered as one of the deadliestcancers because of its extremely aggressive nature and poor survival rate. In IranEsophageal cancer, is the fourth common cancer in women and fifth common cancer in menup to 2012 statistical analysis. Many environmental risk factors have been proposed forESCC but in this study we evaluated the importance of familial risk factors and the role ofgenetic predisposition in ESCC patients. Whole-exome sequencing (WES) has successfullybeen used to identify several disease-gene relationship especially in case of heterogenicdisease. In this work, we performed computational strategies that have been applied toidentify rare/ germline damaging mutations in whole-exome data including R program,filtering strategy, predictional online program such as Sift, Plyphen2 and Provean.Candidatevariants were screened in 50 non disease sample sequence by studying complete genomics.After extensive filtering strategy and functional predictions, we successfully candidated 16variants common in 9 patient and 4 germline rare/damaging variants KCNJ12/KCNJ18, andGPRIN2 in familial ESCC patients based on computational analysis. The previous studyshow that knocking down KCNJ12 or inwardly rectifying K+ channel (Kir2.2), wasresponsible for causing the cell cycle arrest, this show the important roles of this gene incancer malignancy. This study is the first comprehensively analysed germline mutations infamilial ESCC patients. These findings need further functional studies to validate andunderstand the roles of identified mutations in tumorigenesis.

کلیدواژه ها:

Familial Esophageal Squamous Cell Carcinoma ، Whole-Exome Sequencing ، Germline Mutation ، Genetic Predisposition ، Environmental Factors