Landscape of RAS Variations in 17,993 Pan-cancer Patients Identified by Next-generation Sequencing


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.

Fig. 1


  1. 1.

    Vetter IR, Wittinghofer A (2001) The guanine nucleotide-binding switch in three dimensions. Science 294(5545):1299–1304

    Article  CAS  Google Scholar 

  2. 2.

    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

    Article  CAS  Google Scholar 

  3. 3.

    Lartigue JD (2019) New strategies generate optimism for targeting “Undruggable” KRAS. Oncol Live 20:19

    Google Scholar 

  4. 4.

    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

    Article  CAS  Google Scholar 

  5. 5.

    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

    Article  CAS  Google Scholar 

Download references


The authors have not received addition funding to support the production of this article.

Author information



Corresponding authors

Correspondence to Dedian Chen or Hao Wu.

Ethics declarations

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.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

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).

Download citation


  • Carcinoma
  • Genetics
  • RAS gene
  • Next-generation sequencing