大腸息肉可大致分為增生性和腫瘤性。腫瘤性息肉可進一步分為四種亞型（管狀，絨毛管狀，絨毛和無柄鋸齒狀），它們已經失去了一些正常調控的能力，這意味著它們具有更高的機率發展成大腸癌。我們收集五種不同類型息肉的外顯子組定序資料，並希望找出它們的核苷酸變異的差異和拷貝數變異。計算TMB、Ka/Ks及Kt/Ks，及進行突變特徵分析及主成分分析，發現到息肉與正常病例之間無顯著差異，證明息肉仍處於腫瘤發生的早期階段。接下來使用GATK進行大腸息肉變體辨識。我們發現在不同類型的息肉中APC在tubular—villous系列中可能扮，而MSH3可能在hyperplastic—sessile serrated adenoma/polyps 系列中演著早期共同的驅動事件。分析拷貝數改變和基因組不穩定性，發現到在息肉階段已經出現了拷貝數變異及基因組不穩定的現象。最後分析線上公開的定序資料，發現到APC或MSH3變異在息肉RNA定序及大腸癌外顯子組定序資料中同樣也存在，驗證了在我們資料組中的發現。不同系列的息肉所走向癌症的初始路徑可能不一樣，過程中可能由一些共同事件及相異事件可能造成型態上及發展潛能上的異質性。我們預計這樣的分析流程工具將幫助我們了解五種息肉之間的基因改變狀態。

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.

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