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.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Vetter IR, Wittinghofer A (2001) The guanine nucleotide-binding switch in three dimensions. Science 294(5545):1299–1304
Wan XB, Wang AQ, Cao J et al (2019) Relationships among KRAS mutation status, expression of RAS pathway signaling molecules, and clinicopathological features and prognosis of patients with colorectal cancer. World J Gastroenterol 25(7):808–823
Lartigue JD (2019) New strategies generate optimism for targeting “Undruggable” KRAS. Oncol Live 20:19
Chaft JE, Litvak A, Arcila ME et al (2014) Phase II study of the GI-4000 KRAS vaccine after curative therapy in patients with stage I-III lung adenocarcinoma harboring a KRAS G12C, G12D, or G12V mutation. Clin Lung Cancer 15(6):405–410
Shepherd FA, Domerg C, Hainaut P et al (2013) Pooled analysis of the prognostic and predictive effects of KRAS mutation status and KRAS mutation subtype in early-stage resected non-small-cell lung cancer in four trials of adjuvant chemotherapy. J Clin Oncol 31(17):2173–2181
The authors have not received addition funding to support the production of this article.
Conflict of Interest
The authors have no conflicts of interest to declare.
Statement of Ethics
Subjects have given their written informed consent. The authors have no ethical conflicts to disclose.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Zhou, S., Zhang, D., Li, J. et al. Landscape of RAS Variations in 17,993 Pan-cancer Patients Identified by Next-generation Sequencing. Pathol. Oncol. Res. (2020). https://doi.org/10.1007/s12253-020-00845-9
- RAS gene
- Next-generation sequencing