Identification of Survivin Polymorphism in familial esophageal cancer based on Whole-Exome sequencingdata

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancieswith poor prognoses worldwide leading to high mortality rate and poor 5 year survival.Baculoviral IAP repeat containing 5 (BIRC5) also called Survivin is a member of the inhibitorof apoptosis (IAP) gene family, which inhibits caspases activation. It functions as a negativeregulator of programmed cell death. The BIRC5 polymorphisms are involved in geneticpredisposition of a variety of tumors including gastric, colorectal and bladder cancers.Tounderstand the gremline variants in ten familial ESCC patients, Exome sequencing wasperformed on SureSelect target enrichment system. The reads are mapped against UCSChg19. The dbSNP 135 & 1000G were used for population allele frequencies. Singlenucleotide polymorphism (SNP) BIRC5 gene was analyzed.A missense variant (rs2071214)in BIRC5 exon 5 was found in nine of ten analyzed probands with Familiar ESCC.Rs2071214 leads to change of G454A which substitutes 152Glu with Lys in amino acidsequence. This variant is located in C-terminal end of the protein. Various correlationsbetween rs2071214 and increased risk of different cancers was reportedpreviously in Asianspopulation. Recent evidences demonstrated that several factors can regulate the expressionof Survivin such as its genetic variations. The overexpression of Survivin can inhibitapoptosis and increase cell proliferation. The Survivin rs2071214 seems to be associatedwith high risk of incident of familial ESCC.

کلیدواژه ها:

BIRC5 ، Polymorphism ، Esophageal squamous cell carcinoma(ESCC) ، ApoptosisPathway ، Whole Exome sequencing