AUTHOR=Liu Zaoqu , Zhang Yuyuan , Dang Qin , Wu Kunpeng , Jiao Dechao , Li Zhen , Sun Zhenqiang , Han Xinwei 

TITLE=Genomic Alteration Characterization in Colorectal Cancer Identifies a Prognostic and Metastasis Biomarker: FAM83A|IDO1

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.632430

DOI=10.3389/fonc.2021.632430

ISSN=2234-943X

ABSTRACT=<p>Genomic alterations constitute crucial elements of colorectal cancer (CRC). However, a comprehensive understanding of CRC genomic alterations from a global perspective is lacking. In this study, a total of 2,778 patients in 15 public datasets were enrolled. Tissues and clinical information of 30 patients were also collected. We successfully identified two distinct mutation signature clusters (MSC) featured by massive mutations and dominant somatic copy number alterations (SCNA), respectively. MSC-1 was associated with defective DNA mismatch repair, exhibiting more frequent mutations such as <italic>ATM, BRAF</italic>, and <italic>SMAD4</italic>. The mutational co-occurrences of <italic>BRAF</italic>-<italic>HMCN</italic> and <italic>DNAH17</italic>-<italic>MDN1</italic> as well as the methylation silence event of MLH-1 were only found in MSC-1. MSC-2 was linked to the carcinogenic process of age and tobacco chewing habit, exhibiting dominant SCNA such as <italic>MYC</italic> (8q24.21) and <italic>PTEN</italic> (10q23.31) deletion as well as <italic>CCND3</italic> (6p21.1) and <italic>ERBB2</italic> (17q12) amplification. MSC-1 displayed higher immunogenicity and immune infiltration. MSC-2 had better prognosis and significant stromal activation. Based on the two subtypes, we identified and validated the expression relationship of <italic>FAM83A</italic> and <italic>IDO1</italic> as a robust biomarker for prognosis and distant metastasis of CRC in 15 independent cohorts and qRT-PCR data from 30 samples. These results advance precise treatment and clinical management in CRC.</p>