Comparative analysis of clonal evolution among patients with right- and left-sided colon and rectal 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 Wang; Yue Zhang; Kui Wu; Shida Zhu; Lars Bolund; Huanming Yang; Xun Xu; Junnian Liu; Yun Lu; Xin Liu

doi:10.1016/j.isci.2021.102718

Comparative analysis of clonal evolution among patients with right- and left-sided colon and rectal cancer

iScience. 2021 Jun 11;24(7):102718. doi: 10.1016/j.isci.2021.102718. eCollection 2021 Jul 23.

Authors

Santasree Banerjee^{1

2

3}, Xianxiang Zhang⁴, Shan Kuang^{1

3}, Jigang Wang⁵, Lei Li^{1

3

6}, Guangyi Fan^{1

2

3}, Yonglun Luo^{1

2

3

7}, Shuai Sun^{1

2

3}, Peng Han^{1

3}, Qingyao Wu⁴, Shujian Yang⁴, Xiaobin Ji⁵, Yong Li^{1

3}, Li Deng^{1

3

8}, Xiaofen Tian^{2

3

9}, Zhiwei Wang^{1

2

3}, Yue Zhang^{1

3}, Kui Wu^{2

3}, Shida Zhu^{2

3}, Lars Bolund^{1

2

3

7

10}, Huanming Yang^{2

11}, Xun Xu^{1

2

3

12}, Junnian Liu^{1

2

3}, Yun Lu^{4

13}, Xin Liu^{1

2

3}

Affiliations

¹ BGI-Qingdao, BGI-Shenzhen, Qingdao 266555, China.
² BGI-Shenzhen, Shenzhen 518083, China.
³ China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China.
⁴ Department of Gastroenterology, General Surgery Center, The Affiliated Hospital of Qingdao University, Qingdao 266555, China.
⁵ Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266555, China.
⁶ School of Future Technology, University of Chinese Academy of Sciences, Beijing 101408, China.
⁷ Department of Biomedicine, Aarhus University, Aarhus 8000, Denmark.
⁸ State Key Laboratory of Agricultural Genomics, BGI-Shenzhen, Shenzhen 518083, China.
⁹ MGI, BGI-Shenzhen, Shenzhen 518083, China.
¹⁰ Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, BGI-Shenzhen, Qingdao, China.
¹¹ James D. Watson Institute of Genome Sciences, Hangzhou 310058, Zhejiang, China.
¹² Guangdong Provincial Key Laboratory of Genome Read and Write, BGI-Shenzhen, Shenzhen, Guangdong, China.
¹³ Shandong Key Laboratory of Digital Medicine and Computer Assisted Surgery, Qingdao University, Qingdao, China.

Abstract

Tumor multiregion sequencing reveals intratumor heterogeneity (ITH) and clonal evolution playing a key role in tumor progression and metastases. Large-scale high-depth multiregional sequencing of colorectal cancer, comparative analysis among patients with right-sided colon cancer (RCC), left-sided colon cancer (LCC), and rectal cancer (RC), as well as the study of lymph node metastasis (LN) with extranodal tumor deposits (ENTDs) from evolutionary perspective remain weakly explored. Here, we recruited 68 patients with RCC (18), LCC (20), and RC (30). We performed high-depth whole-exome sequencing of 206 tumor regions including 176 primary tumors, 19 LN, and 11 ENTD samples. Our results showed ITH with a Darwinian pattern of evolution and the evolution pattern of LCC and RC was more complex and divergent than RCC. Genetic and evolutionary evidences found that both LN and ENTD originated from different clones. Moreover, ENTD was a distinct entity from LN and evolved later.

Keywords: Cancer Systems Biology; Evolutionary Biology; Genomics.