Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
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.
Oncol Res. 2024 Aug 23;32(9):1429-1438. doi: 10.32604/or.2024.047309. eCollection 2024.
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.
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.
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 . ERBB2alt, KRAS: 50.9% . 25.6%, < 0.05; BRAF: 8.5% . 2.3%, < 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%).
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.
人表皮生长因子受体 2（HER2）靶向治疗已显示出对 HER2 扩增的转移性结直肠癌（mCRC）患者的潜在益处，但在 HER2 突变型 CRC 中并不令人满意。
因此，阐明红细胞生成素 B-2（ERBB2）的扩增和体细胞突变至关重要。对 2454 例中国 CRC 病例进行了全面的基因组分析，以评估 733 个与癌症相关基因中的基因组改变、肿瘤突变负担、微卫星不稳定性和程序性死亡配体 1（PD-L1）表达。
在 2454 例 CRC 患者中，85 例（3.46%）表现出 ERBB2 扩增，55 例（2.24%）携带 ERBB2 突变。在 16 个检测到的突变位点中，p.R678Q（28%）、p.V8421（24%）和 p.S310F/Y（12%）最为常见。与 ERBB2 改变（alt）组相比，KRAS/BRAF 突变在 ERBB2 野生型（wt）样本中更为常见（ERBB2wt. ERBB2alt，KRAS：50.9%. 25.6%，<0.05；BRAF：8.5%. 2.3%，<0.05）。CRC 中 32.7%（18/55）的 ERBB2 突变表现为微卫星不稳定高（MSI-H），而没有 HER2 扩增的病例表现为 MSI-H。突变基因在 ERBB2 拷贝数变异（CNV）和 ERBB2 单核苷酸变异（SNV）之间存在差异；TP53 改变往往与 ERBB2 扩增（92.3%）而非 ERBB2 突变（58.3%）同时发生。KRAS 和 PIK3CA 改变在 ERBB2 SNV 病例中更为常见（KRAS/PIK3CA：45.8%/31.2%），而在 ERBB2 扩增病例中则更为常见（KRAS/PIK3CA：14.1%/7.7%）。
我们的研究描绘了中国大规模 CRC 患者队列中 HER2 改变的情况。这些发现加深了我们对中国 CRC 患者分子特征的理解，并为进一步研究提供了有价值的启示。
