A Comparative Analysis of Individual RAS Mutations in Cancer Biology

Carmen Muñoz-Maldonado; Yitzhak Zimmer; Michaela Medová

doi:10.3389/fonc.2019.01088

A Comparative Analysis of Individual RAS Mutations in Cancer Biology

Front Oncol. 2019 Oct 18:9:1088. doi: 10.3389/fonc.2019.01088. eCollection 2019.

Authors

Carmen Muñoz-Maldonado^{1

2}, Yitzhak Zimmer^{1

2}, Michaela Medová^{1

2}

Affiliations

¹ Department of Radiation Oncology, Inselspital, Bern University Hospital, Bern, Switzerland.
² Radiation Oncology, Department for BioMedical Research, University of Bern, Bern, Switzerland.

Abstract

In human cells, three closely related RAS genes, termed HRAS, KRAS, and NRAS, encode four highly homologous proteins. RAS proteins are small GTPases involved in a broad spectrum of key molecular and cellular activities, including proliferation and survival among others. Gain-of-function missense mutations, mostly located at codons 12, 13, and 61, constitutively activate RAS proteins and can be detected in various types of human cancers. KRAS is the most frequently mutated, followed by NRAS and HRAS. However, each isoform exhibits distinctive mutation frequency at each codon, supporting the hypothesis that different RAS mutants may lead to distinct biologic manifestations. This review is focused on the differences in signaling and phenotype, as well as on transcriptomics, proteomics, and metabolomics profiles related to individual RAS-mutated variants. Additionally, association of these mutants with particular targeted outcomes and rare mutations at additional RAS codons are discussed.

Keywords: GTP/GDP binding; RAS mutations; RAS profile; RAS signaling; RAS-mutated cancers; RAS-related omics; rare codons; treatment responses.

Publication types

Review