ARID1A peptide

AT-rich interaction domain containing protein 1A (ARID1A), has recently emerged as a novel class of gene which acts as a potent tumor suppressor in numerous types of cancers such as Gastric, Breast, Ovarian, Colorectal, Lung cancers. ARID1A is involved in the regulation of various cellular processes such as proliferation, differentiation and DNA repair, yet its association with the susceptibility of cancer remains unknown. Here, we aimed to analyse the association of the ARID1A variants (Pro912Thr, Gln944Lys and Gln920Ter) with the risk of Gastric cancer (GC) in Kashmiri population. The study included 103 confirmed cases of GC and 163 normal controls. The genotypes were studied using Polymerase Chain Reaction. Different bioinformatic predictive tools were also used to analyse the possible effect of these SNP's on the resultant protein. The Pro912Thr and Gln920Ter variants of ARID1A showed significant difference in genotypic and allelic frequencies between the GC cases and controls (P < 0.05), whereas, the data did not reveal any correlation between Gln944Lys variant and Gastric cancer risk. Both Pro912Thr and Gln920Ter SNP's follow "Dominant mode of inheritance". In Silico analysis predicted that amino acid substitution of Pro912Thr SNP decreases the protein stability thus changing the functional properties of resultant protein, so backing the possibility of damaging effect of this SNP. Our study suggests that Pro912Thr and Gln920Ter SNP's of ARD1A gene are associated with increased risk of GC in Kashmiri population.

BackgroundHepatocellular carcinoma (HCC) recurrently develops in cirrhotic liver containing a number of regenerative nodules (RNs). However, the biological tumorigenic potential of RNs is still unclear. To uncover the molecular bases of tumorigenesis in liver cirrhosis, we investigated the genetic aberrations in RNs of cirrhotic tissues using next-generation sequencing.MethodsWe isolated 205 RNs and 7 HCC tissues from the whole explanted livers of 10 randomly selected patients who had undergone living-donor liver transplantation. Whole-exome sequencing and additional targeted deep sequencing on 30 selected HCC-related genes were conducted to reveal the mutational landscape of RNs and HCCs.ResultsWhole-exome sequencing demonstrated that RNs frequently harbored relatively high-abundance genetic alterations, suggesting a clonal structure of each RN in cirrhotic liver. The mutation signature observed in RNs was similar to those determined in HCC, characterized by a predominance of C>T transitions, followed by T>C and C>A mutations. Targeted deep sequencing analyses of RNs identified nonsynonymous low-abundance mutations in various tumor-related genes, including TP53 and ARID1A. In contrast, TERT promoter mutations were not detected in any of the RNs examined. Consistently, TERT expression levels in RNs were comparable to those in normal livers, whereas every HCC tissue demonstrated an elevated level of TERT expression.ConclusionAnalyses of RNs constructing cirrhotic liver indicated that a variety of genetic aberrations accumulate in the cirrhotic liver before the development of clinically and histologically overt HCC. These aberrations in RNs could provide the basis of tumorigenesis in patients with liver cirrhosis.