Galactophore Department, The Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital) , No.518 Kunzhou Road, Yunnan Province, 650118, Kunming, China.
The Medical Department, 3D Medicines Inc, Shanghai, China.
Pathol Oncol Res. 2020 Oct;26(4):2835-2837. doi: 10.1007/s12253-020-00845-9. Epub 2020 Jun 30.
RAS family genes (HRAS, KRAS and NRAS) were frequently observed in several tumors. The expression of constitutively active RAS proteins mediated by RAS variations promote the development of tumors. KRAS is an important prognostic and drug resistance biomarker. It would also be a promising drug target. Several trials which evaluating the efficacy of RAS G12C inhibitor in solid tumors are initiated. Herein, we analyzed the alterations status of KRAS/NRAS/HRAS across diverse solid tumors. The sing nucleotide variants (SNV) and copy number variants (CNV) data of 17993 Chinese patients from 22 types of cancer were obtained in our database. Genomic profiling of DNA was performed through a next-generation sequencing on tissue. Only the pathogenic mutations and likely pathogenic mutations in clinical significance were rolled into our analysis. Among 17993 pan-cancer patients, the total RAS variants frequency was 22.58%. KRAS was the most frequently altered, followed by NRAS and HRAS. For the SNV, KRAS were most commonly found in pancreas cancer, intestine cancer and colorectal cancer. Further analysis among KRAS SNV patients showed that the mutation frequency of KRAS G12C, G12D, G12R, and G12V was 1.81%, 6.81%, 0.69% and 4.25%, respectively. A total of 21 in 22 types of solid tumors had KRAS G12C/D/R/V pathogenic or likely pathogenic mutation, which occurred most frequently in colorectal cancer, pancreas cancer and lung cancer. Our results suggested that a variety of solid tumors may harbor KRAS G12C/D/R/V mutation. These patients may benefit from KRAS inhibitors.
RAS 家族基因（HRAS、KRAS 和 NRAS）在多种肿瘤中经常被观察到。RAS 变异导致组成性激活的 RAS 蛋白的表达促进了肿瘤的发展。KRAS 是一个重要的预后和耐药生物标志物，也是一个很有前途的药物靶点。目前已经启动了几项评估 RAS G12C 抑制剂在实体瘤中的疗效的临床试验。在此，我们分析了不同实体瘤中 KRAS/NRAS/HRAS 的改变状态。从我们的数据库中获得了来自 22 种癌症的 17993 名中国患者的单核苷酸变异（SNV）和拷贝数变异（CNV）数据。通过组织的下一代测序对 DNA 进行了基因组分析。只有具有临床意义的致病性突变和可能的致病性突变才被纳入我们的分析。在 17993 名泛癌患者中，总 RAS 变异频率为 22.58%。KRAS 是最常改变的基因，其次是 NRAS 和 HRAS。对于 SNV，KRAS 最常见于胰腺癌、肠癌和结直肠癌。对 KRAS SNV 患者的进一步分析表明，KRAS G12C、G12D、G12R 和 G12V 的突变频率分别为 1.81%、6.81%、0.69%和 4.25%。在 22 种实体肿瘤中，共有 21 种存在 KRAS G12C/D/R/V 致病性或可能致病性突变，最常发生于结直肠癌、胰腺癌和肺癌。我们的研究结果表明，多种实体肿瘤可能存在 KRAS G12C/D/R/V 突变，这些患者可能从 KRAS 抑制剂中获益。
