Intratumor Heterogeneity and Evolution of Colorectal Cancer

Santasree Banerjee; Xianxiang Zhang; Shan Kuang; Jigang Wang; Lei Li; Guangyi Fan; Yonglun Luo; Shuai Sun; Peng Han; Qingyao Wu; Shujian Yang; Xiaobin Ji; Yong Li; Li Deng; Xiaofen Tian; Zhiwei Peter Wang; Yue Zhang; Kui Wu; Shida Zhu; Lars Bolund; Huanming Yang; Xun Xu; Junnian Liu; Yun Lu; Xin Liu

doi:10.1101/2020.01.13.904276

GeneticsbioRxivJan 13, 2020

Preprint

Intratumor Heterogeneity and Evolution of Colorectal Cancer

Santasree Banerjee iD, Xianxiang Zhang iD, Shan Kuang iD, Jigang Wang iD, Lei Li iD, Guangyi Fan iD, Yonglun Luo iD, Shuai Sun iD, Peng Han iD, Qingyao Wu iD, Shujian Yang, Xiaobin Ji iD, Yong Li, Li Deng iD, Xiaofen Tian, Zhiwei Peter Wang iD, Yue Zhang iD, Kui Wu iD, Shida Zhu iD, Lars Bolund iD, Huanming Yang iD, Xun Xu iD, Junnian Liu iD, Yun Lu iD, Xin Liu iD

Abstract

Intratumor heterogeneity (ITH) enable us to understand the evolution of cancer. ITH and evolution of colorectal cancer (CRC) has not been well studied. In this prospective study, we recruited different stages of 68 CRC patients with primary tumor at right-sided colon, left-sided colon and rectum. We performed high-depth whole exome sequencing of 206 multi-region tumor samples including primary tumors, lymph node metastasis (LN) and extranodal tumor deposits (ENTD). Our result showed extreme ITH with Darwinian pattern of CRC evolution, evolution pattern of left-sided CRC was more complex and divergent than right-sided CRC and both LN and ENTD were of polyclonal in origin. Extensive ITH was found in driver mutations in KRAS and PIK3CA genes, suggesting major limitations of single biopsies in clinical diagnosis for the CRC patients. In conclusion, our study showed the Darwinian pattern of CRC evolution with differences in evolution pattern between right-sided and left-sided CRC patients.

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