Systematic investigation of the prognostic impact of clonal status of somatic mutations across multiple cancer types

Peng Cheng; Yujia Lan; Jianlong Liao; Erjie Zhao; Haoteng Yan; Liwen Xu; Suru A; Yanyan Ping; Jinyuan Xu

doi:10.1016/j.ygeno.2022.110412

Systematic investigation of the prognostic impact of clonal status of somatic mutations across multiple cancer types

Genomics. 2022 Jul;114(4):110412. doi: 10.1016/j.ygeno.2022.110412. Epub 2022 Jun 15.

Authors

Peng Cheng¹, Yujia Lan¹, Jianlong Liao¹, Erjie Zhao¹, Haoteng Yan², Liwen Xu¹, Suru A¹, Yanyan Ping³, Jinyuan Xu⁴

Affiliations

¹ College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
² College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China; Advanced Innovation Center for Human Brain Protection, and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China.
³ College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China. Electronic address: pingyanyan@hrbmu.edu.cn.
⁴ College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China. Electronic address: xujinyuan@hrbmu.edu.cn.

PMID: 35714828
DOI: 10.1016/j.ygeno.2022.110412

Abstract

Tumors are genetically heterogeneous and many mutations are actually present in subclonal populations. The clonal status of mutations is valuable for accurate prognosis, clinical management. The aim of this study was to identify the clonal status of somatic mutations and systematically evaluate their prognostic values across various cancer types. We totally identified 227 clonal and 432 subclonal mutations contributed to prognosis and demonstrated the importance of clonal status in improving mutation-related clinical guidance. We further developed a customized multi-step approach to identify gene-specific prognostic patterns of clonal status at pan-cancer level and found some cancer-specific prognostic patterns. The 'subclonal-dependent risk' subpattern was one of the most common subpatterns, it usually accompanied by high genomic in-stability and high extent of intra-tumor heterogeneity and could be used to improve the accuracy of prognostic analysis. Our results revealed the importance of clonal status, especially subclonal mutation in clinical survival.

Keywords: Clonal status; Intra-tumor heterogeneity; Prognosis; Risk stratification; Subclonal mutation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Clonal Evolution
Genomics
Humans
Mutation
Neoplasms* / genetics
Neoplasms* / pathology
Prognosis