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

Journal of Translational Medicine

Chun-He Yang¹  Meng-Huan Zhang¹  Xiao-Luan Yan²  Juan Li²  Ke-Min Jin²  Bao-Cai Xing²  Kun Wang²  Hong-Wei Wang²  Li-Jun Wang²  Quan Bao² 

[1] GloriousMed Clinical Laboratory (Shanghai) Co., Ltd, Shanghai, China;Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Haidian District, Beijing, China;

关键词: Colorectal cancer;    Liver metastases;    Genomic alterations;    Heterogeneity;    Targeted sequencing;   

DOI  :  10.1186/s12967-021-02986-0

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsA 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.ResultsIn 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.ConclusionWe provide a comprehensive depiction of the genomic alterations in Chinese patients with CRLM, providing a fundamental basis for further personalized therapy applications.

【 授权许可】

CC BY