@Article{or.2024.047309,
AUTHOR = {YUZHI LIU, EVELYNE BISCHOF, ZHIQIN CHEN, JIAHUAN ZHOU, BEI ZHANG, DING ZHANG, YONG GAO, MING QUAN},
TITLE = {Genomic profiling of colorectal cancer in large-scale Chinese patients: amplification and somatic mutations in ERBB2},
JOURNAL = {Oncology Research},
VOLUME = {32},
YEAR = {2024},
NUMBER = {9},
PAGES = {1429--1438},
URL = {http://www.techscience.com/or/v32n9/57722},
ISSN = {1555-3906},
ABSTRACT = { <b>Objectives:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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 <i>vs</i>. ERBB2alt, KRAS: 50.9% <i>vs</i>. 25.6%, <i>p</i> < 0.05; BRAF: 8.5% <i>vs</i>. 2.3%, <i>p</i> < 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%). <b>Conclusion:</b> 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.},
DOI = {10.32604/or.2024.047309}
}