RAS Mutations and Oncogenesis: Not all RAS Mutations are Created Equally

Miller, Mark Steven; Miller, Lance D.

doi:10.3389/fgene.2011.00100

Cited by 77Protein Kinase Regulation and GTPase SignalingProtein Tyrosine PhosphatasesMelanoma and MAPK Pathways

RAS Mutations and Oncogenesis: Not all RAS Mutations are Created Equally

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Miller, Mark Steven, Miller, Lance D.·2012·Frontiers in Genetics

DOI 10.3389/fgene.2011.00100PMC PMC3262225

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Abstract

Mutation in RAS proteins is one of the most common genetic alterations observed in human and experimentally induced rodent cancers. In vivo, oncogenic mutations have been shown to occur at exons 12, 13, and 61, resulting in any 1 of 19 possible point mutations in a given tumor for a specific RAS isoform. While some studies have suggested a possible role of different mutant alleles in determining tumor severity and phenotype, no general consensus has emerged on the oncogenicity of different mutant alleles in tumor formation and progression. Part of this may be due to a lack of a single, signature pathway that shows significant alterations between different mutations. Rather, it is likely that subtle differences in the activation, or lack thereof, of downstream effectors by different RAS mutant alleles may determine the eventual outcome in terms of tumor phenotype. This paper reviews our current understanding of the potential role of different RAS mutations on tumorigenesis, highlights studies in model cell culture and in vivo systems, and discusses the potential of expression array and computational network modeling to dissect out differences in activated RAS genes in conferring a transforming phenotype.

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Previous studies have documented substantial differences in the biochemical and signaling properties of the common KRAS variants.
“Previous studies have documented substantial differences in the biochemical and signaling properties of the common KRAS variants (reviewed by Miller et al.5 and Li et al.6).”
From The origins and genetic interactions of KRAS mutations are allele- and tissue-specific (2021) · cites this paper as [5]

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Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer
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KRAS Dimerization Impacts MEK Inhibitor Sensitivity and Oncogenic Activity of Mutant KRAS
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Targeting the KRAS variant for treatment of non-small cell lung cancer: potential therapeutic applications
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Dimerization of the kinase ARAF promotes MAPK pathway activation and cell migration
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The K-Ras, N-Ras, and H-Ras Isoforms: Unique Conformational Preferences and Implications for Targeting Oncogenic MutantsPreprint
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The Ins and Outs of RAS Effector Complexes
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Characterization of distinct types of KRAS mutation and its impact on first‑line platinum‑based chemotherapy in Chinese patients with advanced non‑small cell lung cancer
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The importance of Ras in drug resistance in cancer
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Comprehensive survey of HRAS, KRAS, and NRAS mutations in proliferative thyroid lesions from an ethnically diverse population.
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Metabolic characterization of colorectal cancer cells harbouring different KRAS mutations in codon 12, 13, 61 and 146 using human SW48 isogenic cell lines
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Evaluation of Emergent Mutations in Circulating Cell-Free DNA and Clinical Outcomes in Patients with Metastatic Colorectal Cancer Treated with Panitumumab in the ASPECCT Study
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The PI3K-AKT-mTOR axis persists as a therapeutic dependency in KRASG12D-driven non-small cell lung cancer
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A novel MTORC2-AKT-ROS axis triggers mitofission and mitophagy-associated execution of colorectal cancer cells upon drug-induced activation of mutant KRAS
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Multiplexed screens identify RAS paralogues HRAS and NRAS as suppressors of KRAS-driven lung cancer growth
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The prevalence and prognostic significance of KRAS mutation in bladder cancer, chronic myeloid leukemia and colorectal cancer
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The mutational spectrum of HRAS, KRAS, NRAS and FGFR3 genes in bladder cancer
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Regulated proteolysis of <scp>C</scp> andida albicans <scp>R</scp> as1 is involved in morphogenesis and quorum sensing regulation
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Investigation of GTP-dependent dimerization of G12X K-Ras variants using ultraviolet photodissociation mass spectrometry
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Novel regulation of Ras proteins by direct tyrosine phosphorylation and dephosphorylation
Buday, L., & Vas, V. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09918-2 · Cited by 30 · see citing works
How cells sense and integrate information from different sources
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Monoubiquitination in Homeostasis and Cancer
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The Cell Transformation Assay: A Historical Assessment of Current Knowledge of Applications in an Integrated Approach to Testing and Assessment for Non-Genotoxic Carcinogens
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Multiclonal complexity of pediatric acute lymphoblastic leukemia and the prognostic relevance of subclonal mutations
Antić, Ž., Yu, J., van Reijmersdal, S. V., van Dijk, A. H. A., Dekker, L., Segerink, W. H., Sonneveld, E., Fiocco, M. F., Pieters, R., Hoogerbrugge, P. M., et al. (2020) · Haematologica · doi:10.3324/haematol.2020.259226 · Cited by 22 · see citing works
Expression of Abelson Interactor 1 (Abi1) Correlates with Inflammation, KRAS Mutation and Adenomatous Change during Colonic Carcinogenesis
Steinestel, K., Brüderlein, S., Steinestel, J., Märkl, B., Schwerer, M. J., Arndt, A., Kraft, K., Pröpper, C., & Möller, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040671 · Cited by 21 · see citing works
Clinical update on K-Ras targeted therapy in gastrointestinal cancers
Pant, S., Hubbard, J. M., Martinelli, E., & Bekaii‐Saab, T. (2018) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2018.07.011 · Cited by 21 · see citing works
Bilateral blockade of MEK- and PI3K-mediated pathways downstream of mutant KRAS as a treatment approach for peritoneal mucinous malignancies
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Pan-KRAS inhibitors suppress proliferation through feedback regulation in pancreatic ductal adenocarcinoma
Wang, C.-X., Wang, T., Zhang, K.-D., Li, M., Shen, Q., Lu, S., & Zhang, J. (2022) · Acta Pharmacologica Sinica · doi:10.1038/s41401-022-00897-4 · Cited by 16 · see citing works
The Inhibition of Wnt Restrain KRASG12V-Driven Metastasis in Non-Small-Cell Lung Cancer
Hung, P.-S., Huang, M.-H., Kuo, Y., & Yang, J. C. (2020) · Cancers · doi:10.3390/cancers12040837 · Cited by 14 · see citing works
Retrospective Comparative Analysis of KRAS G12C vs. Other KRAS Mutations in mCRC Patients Treated With First-Line Chemotherapy Doublet + Bevacizumab
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H‐Ras Transformation of Mammary Epithelial Cells Induces ERK‐Mediated Spreading on Low Stiffness Matrix
Plunkett, C. M., Kumar, A., Yrastorza, J., Hou, Y., Placone, J. K., Grennan, G., & Engler, A. J. (2020) · Advanced Healthcare Materials · doi:10.1002/adhm.201901366 · Cited by 11 · see citing works
New insights into RAS in head and neck cancer
Jagadeeshan, S., Novoplansky, O., Cohen, O. M., Kurth, I., Heß, J., Rosenberg, A. J., Grandis, J. R., & Elkabets, M. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.188963 · Cited by 10 · see citing works
Atypical RAS Mutations in Metastatic Colorectal Cancer
Pietrantonio, F., Yaeger, R., Schrock, A. B., Randon, G., Romero-Cordoba, S. L., Rossini, D., Fucà, G., Ross, J. S., Kotani, D., Madison, R., et al. (2019) · JCO Precision Oncology · doi:10.1200/po.19.00136 · Cited by 10 · see citing works
A Novel HRAS Mutation Independently Contributes to Left Ventricular Hypertrophy in a Family with a Known MYH7 Mutation
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High-Complexity shRNA Libraries and PI3 Kinase Inhibition in Cancer: High-Fidelity Synthetic Lethality Predictions
Mues, M., Karra, L., Romero–Moya, D., Wandler, A. M., Hangauer, M. J., Ksionda, O., Thus, Y. J., Lindenbergh, M. F., Shannon, K., McManus, M. T., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.03.045 · Cited by 10 · see citing works
Effects of Hudson River Stressors on Atlantic Tomcod: Contaminants and a Warming Environment
Wirgin, I. I., Chambers, R. C., Waldman, J. R., Roy, N. K., Witting, D. A., & Mattson, M. T. (2023) · Reviews in Fisheries Science & Aquaculture · doi:10.1080/23308249.2023.2189483 · Cited by 8 · see citing works
2′-Deoxy Guanosine Nucleotides Alter the Biochemical Properties of Ras
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Phosphorylated nuclear DICER1 promotes open chromatin state and lineage plasticity of AT2 tumor cells in lung adenocarcinomas
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Isoform-Specific Effects of Wild-Type Ras Genes on Carcinogen-Induced Lung Tumorigenesis in Mice
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Authors: Miller, M. S., & Miller, L. D.
Affiliations: Wake Forest Baptist Comprehensive Cancer Center (US)
Wake Forest University Health Sciences (US)
Corresponding author: Miller, Mark Steven
ORCID: Miller, Mark Steven
Miller, Lance D.
Venue: Frontiers in Genetics
Publisher: Frontiers Media SA
Published: 2012
Volume: 2
Pages: 100-100
ISSN: 1664-8021 (ISSN-L)
DOI: 10.3389/fgene.2011.00100
PMC: PMC3262225
OpenAlex: W1988100553
Cited by: 76
References: 118
Citations by year: 2026: 1 · 2025: 4 · 2024: 7 · 2023: 10 · 2022: 6 · 2021: 9 · 2020: 11 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 5
FWCI: 1.67
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc
Locations: Frontiers in Genetics (publishedVersion, cc-by-nc)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Wake Forest University
National Cancer Institute (CA 12197, R01CA136910, P30CA012197, P30 CA 12197)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Keywords: RAS mutations, carcinogenesis, Ras isoforms, point mutations, mutant allele, tumor progression, tumor severity, gene expression profiling

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RAS Mutations and Oncogenesis: Not all RAS Mutations are Created Equally

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