Whole exome sequence analysis of colorectal polyps to study the development of colorectal cancer

Abstract

There are two common types of colon polyps (hyperplastic and neoplastic) The neoplastic polyp can be further classified into four subtypes (tubular tubulovillous villous and sessile serrated (SSA/Ps)) and they have lost some regulation which means they have higher potential to develop into colon cancer Five different types of polyps’ exome sequencing data were collected and hoped to figure out their nucleotide variant events and copy number alteration (CNA) Different mechanisms will generate different mutational processes and these unique combinations of mutation types call mutational signatures We used the online tool to do the mutational signature analysis and principal component analysis and found that there was no significant difference between polyps and normal cases which prove that polyps still at the very early stage in tumorigenesis We also introduced Genome Analysis Toolkit (GATK) to analyze alteration in colon polyps Between the different type of polyps we discovered that APC or MSH3 may play an important part in the early stage of tumorigenesis of CRC Next we applied CNVkit to infer the CNA and genomic instability and found that copy number variation and genomic instability have occurred in the polyp stage Finally we downloaded the RNA sequencing cohort data from the SRA database to validate the phenomenon we discovered before by analyzing the variants These variant events were also found in the different stage of CRC data (downloaded from TCGA) We expect these tools will help us to understand the gene alteration status between five types of polyps

Date of Award	2019
Original language	English
Supervisor	Ta-Chien Tseng (Supervisor)