Wu Liyuan, Rao Wei, Guo Lei, Zhang Fanshuang, Li Weihua, Ying Jianming
Departments of Pathology, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17 Panjiayuan Nanli, Beijing, 100021, China.
J Cancer Res Clin Oncol. 2025 Feb 27;151(2):94. doi: 10.1007/s00432-025-06118-9.
The Kirsten rat sarcoma viral oncogene (KRAS) is the most frequently mutated oncogene in human cancers. Significant advancements have been made in targeted therapy and immunotherapy for this gene in recent years, underscoring the importance of comprehensively understanding the genomic landscape of KRAS across various cancer types.
Using next-generation sequencing (NGS) technology and a panel of 520 genes, KRAS mutations, tumor mutation burden (TMB), and microsatellite instability (MSI-H) status were investigated.
An analysis of 10,820 tumor samples found KRAS mutations in 19.97% of cases. Pancreatic cancer showed the highest prevalence of KRAS mutations at 73.51%, while colorectal at 41.45%, uterine at 21.23%, and lung cancer at 11.24%. KRAS G12D mutation is most common in pancreatic, colorectal, and gastric cancers, while KRAS G12V mutation is predominant in uterine cancer, and KRAS G12C mutation is most frequent in lung cancer. Significant correlations were found between TMB and KRAS G13D/G12V mutations in colorectal cancer. KRAS G13D notably affected TMB in uterus cancer, while KRAS G12C mutation was linked to high TMB in lung cancer. Moreover, statistical analysis revealed a significant association between KRAS G13D/G12V mutations and MSI-H in colorectal cancer.
KRAS mutations were most frequent in cancers of the digestive, female reproductive, and respiratory systems. Specific KRAS mutations are associated with TMB and MSI in various cancer types.
Kirsten大鼠肉瘤病毒癌基因（KRAS）是人类癌症中最常发生突变的癌基因。近年来，针对该基因的靶向治疗和免疫治疗取得了重大进展，这凸显了全面了解KRAS在各种癌症类型中的基因组格局的重要性。
使用下一代测序（NGS）技术和一组520个基因，研究了KRAS突变、肿瘤突变负荷（TMB）和微卫星不稳定性（MSI-H）状态。
对10820个肿瘤样本的分析发现，19.97%的病例存在KRAS突变。胰腺癌的KRAS突变发生率最高，为73.51%，而结直肠癌为41.45%，子宫癌为21.23%，肺癌为11.24%。KRAS G12D突变在胰腺癌、结直肠癌和胃癌中最常见，而KRAS G12V突变在子宫癌中占主导地位，KRAS G12C突变在肺癌中最常见。在结直肠癌中，TMB与KRAS G13D/G12V突变之间存在显著相关性。KRAS G13D在子宫癌中显著影响TMB，而KRAS G12C突变与肺癌中的高TMB相关。此外，统计分析显示结直肠癌中KRAS G13D/G12V突变与MSI-H之间存在显著关联。
KRAS突变在消化系统、女性生殖系统和呼吸系统癌症中最为常见。特定的KRAS突变与各种癌症类型中的TMB和MSI相关。
