AUTHOR=Zhu Chunrong , Zhu Liangjun , Gu Yanhong , Liu Ping , Tong Xiaoling , Wu Guozhong , Zhu Wenyu , Shen Wenxiang , Bao Hua , Ma Xiangyuan , Yu Ruoying , Wu Xue , Zhu Dongqin , Shu Yongqian , Feng Jifeng 

TITLE=Genomic Profiling Reveals the Molecular Landscape of Gastrointestinal Tract Cancers in Chinese Patients

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.608742

DOI=10.3389/fgene.2021.608742

ISSN=1664-8021

ABSTRACT=<p>Gastrointestinal tract cancers have high incidence and mortality in China, but their molecular characteristics have not been fully investigated. We sequenced 432 tumor samples from the colorectum, stomach, pancreas, gallbladder, and biliary tract to investigate cancer-related mutations and detail the landscape of microsatellite instability (MSI), tumor mutation burden (TMB), and chromosomal instability (CIN). We observed the highest TMB in colorectal and gastric cancers and the lowest TMB in gastrointestinal stromal tumors (GISTs). Twenty-four hyper-mutated tumors were identified only in colorectal and gastric cancers, with a significant enrichment of mutations in the polymerase genes (<italic>POLE</italic>, <italic>POLD1</italic>, and <italic>POLH</italic>) and mismatch repair (MMR) genes. Additionally, CIN preferentially occurred in colorectal and gastric cancers, while pancreatic, gallbladder, and biliary duct cancers had a much lower CIN. High CIN was correlated with a higher prevalence of malfunctions in chromosome segregation and cell cycle genes, including the copy number loss of <italic>WRN</italic>, <italic>NAT1</italic>, <italic>NF2</italic>, and <italic>BUB1B</italic>, and the copy number gain of <italic>MYC</italic>, <italic>ERBB2</italic>, <italic>EGFR</italic>, and <italic>CDK6</italic>. In addition, <italic>TP53</italic> mutations were more abundant in high-CIN tumors, while <italic>PIK3CA</italic> mutations were more frequent in low-CIN tumors. In colorectal and gastric cancers, tumors with MSI demonstrated much fewer copy number changes than microsatellite stable (MSS) tumors. In colorectal and gastric cancers, the molecular characteristics of tumors revealed the mutational diversity between the different anatomical origins of tumors. This study provides novel insights into the molecular landscape of Chinese gastrointestinal cancers and the genetic differences between tumor locations, which could be useful for future clinical patient stratification and targeted interventions.</p>