Characterization of genomic alterations in Chinese colorectal cancer patients with liver metastases

作者：Hongwei Wang, Xiaoluan Yan, Lijun Wang, Meng-Huan Zhang, Chunhe Yang, WeiLiu, Kemin Jin, Quan Bao, Juan Li, Kun Wang, Baocai Xing · 发表于：Journal of Translational Medicine · 年份：2021 · DOI：10.1186/s12967-021-02986-0 · 被引用次数：14 · 研究领域：Colorectal Cancer Treatments and Studies、Hepatocellular Carcinoma Treatment and Prognosis、Cancer Genomics and Diagnostics

BACKGROUND: The exploration of genomic alterations in Chinese colorectal liver metastasis (CRLM) is limited, and corresponding genetic biomarkers for patient's perioperative management are still lacking. This study aims to understand genome diversification and complexity that developed in CRLM. METHODS: A custom-designed IDT capture panel including 620 genes was performed in the Chinese CRLM cohort, which included 396 tumor samples from metastatic liver lesions together with 133 available paired primary tumors. RESULTS: In this Chinese CRLM cohort, the top-ranked recurrent mutated genes were TP53 (324/396, 82%), APC (302/396, 76%), KRAS (166/396, 42%), SMAD4 (54/396, 14%), FLG (52/396, 13%) and FBXW7 (43/396, 11%). A comparison of CRLM samples derived from left- and right-sided primary lesions confirmed that the difference in survival for patients with different primary tumor sites could be driven by variations in the transforming growth factor β (TGF-β), phosphatidylinositol 3-kinase (PI3K) and RAS signaling pathways. Certain genes had a higher variant rate in samples with metachronous CRLM than in samples with simultaneous metastasis. Overall, the metastasis and primary tumor samples displayed highly consistent genomic alterations, but there were some differences between individually paired metastases and primary tumors, which were mainly caused by copy number variations. CONCLUSION: We provide a comprehensive depiction of the genomic alterations in Chinese patients with CR...