Abstract 5284: Characterizing the differences of allelic imbalance between tumor and normal tissues by next-generation sequencing

Abstract

Abstract Genetic variation has proved to contribute to tumor formation. One of the phenomenon caused by genetic variation, allelic imbalance, means different expression abundance between two alleles, recently has become a special landmark on cancer biology, with high prevalence in recent cancer studies. However, the present of allelic imbalance has not been fully understood yet. Taking the advantages of next generation sequencing, allelic imbalance can be identified and quantified through bioinformatics algorithms. Here, we developed a mathematical model to identify with allelic imbalance by concurrently analyzing RNA-Seq and DNA-Seq. First we called heterozygous SNP variants from both RNA-Seq and Exome-Seq data. The allele ratio is counted by the ratio of read depth between two alleles after integrating SNPs into gene level. Next, we identify allelic imbalance genes by differences of RNA and DNA allele ratios between tumor and normal samples. As results, a total of 91143 SNPs were identified in Exome-Seq, and about 3% (2586 out of 91143) SNPs were heterozygous in both tumor and normal tissues. We found that about 118 allelic imbalance genes in tumor tissue are significantly different from those in normal tissue. Furthermore, we investigate the enriched function of these allelic imbalance genes. These result showed that these genes are significantly enriched in DNA repair pathway. We speculated that allelic imbalance in tumor tissue may be involved in the dysregulation of DNA repair. Also other enriched functions were identified, such as z-finger protein pathway. Our goal is to investigate the landscape of allelic imbalance between tumor sample and normal sample. Our results demonstrate the role of allelic imbalance of dysregulation of tumor. Moreover, our method can be applied to uncover more basic mechanisms on allelic imbalance and tumorigenesis. Citation Format: Yao-Wei Jheng, Yu-Chiao Chiu, Tzu-Pin Lu, Liang-Chuan Lai, Mong-Hsun Tsai, Tzu-Hung Hsiao, Eric Y Chuang. Characterizing the differences of allelic imbalance between tumor and normal tissues by next-generation sequencing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5284.