Open Access

ARTICLE

Genomic profiling of colorectal cancer in large-scale Chinese patients: amplification and somatic mutations in ERBB2

by YUZHI LIU^1,#, EVELYNE BISCHOF^2,#, ZHIQIN CHEN¹, JIAHUAN ZHOU³, BEI ZHANG⁴, DING ZHANG⁴, YONG GAO^1,*, MING QUAN^1,*

1 Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
2 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
3 Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China
4 3D Medicines Inc., Shanghai, China

* Corresponding Authors: YONG GAO. Email: ; MING QUAN. Email:

Oncology Research 2024, 32(9), 1429-1438. https://doi.org/10.32604/or.2024.047309

Received 01 November 2023; Accepted 01 March 2024; Issue published 23 August 2024

Abstract

Objectives: Human epidermal growth factor receptor 2 (HER2)-targeted therapies have demonstrated potential benefits for metastatic colorectal cancer (mCRC) patients with HER2 amplification, but are not satisfactory in cases of HER2 mutant CRCs. Methods: Consequently, further elucidation of amplifications and somatic mutations in erythroblastic oncogene B-2 (ERBB2) is imperative. Comprehensive genomic profiling was conducted on 2454 Chinese CRC cases to evaluate genomic alterations in 733 cancer-related genes, tumor mutational burden, microsatellite instability, and programmed death ligand 1 (PD-L1) expression. Results: Among 2454 CRC patients, 85 cases (3.46%) exhibited ERBB2 amplification, and 55 cases (2.24%) carried ERBB2 mutation. p.R678Q (28%), p.V8421 (24%), and p.S310F/Y (12%) were the most prevalent of the 16 detected mutation sites. In comparison to the ERBB2 altered (alt) group, KRAS/BRAF mutations were more prevalent in ERBB2 wild-type (wt) samples (ERBB2wt vs. ERBB2alt, KRAS: 50.9% vs. 25.6%, p < 0.05; BRAF: 8.5% vs. 2.3%, p < 0.05). 32.7% (18/55) of CRCs with ERBB2 mutation exhibited microsatellite instability high (MSI-H), while no cases with HER2 amplification displayed MSI-H. Mutant genes varied between ERBB2 copy number variation (CNV) and ERBB2 single nucleotide variant (SNV); TP53 alterations tended to co-occur with ERBB2 amplification (92.3%) as opposed to ERBB2 mutation (58.3%). KRAS and PIK3CA alterations were more prevalent in ERBB2 SNV cases (KRAS/PIK3CA: 45.8%/31.2%) compared to ERBB2 amplification cases (KRAS/PIK3CA: 14.1%/7.7%). Conclusion: Our study delineates the landscape of HER2 alterations in a large-scale cohort of CRC patients from China. These findings enhance our understanding of the molecular features of Chinese CRC patients and offer valuable implications for further investigation.

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