Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Jan 3:2:100.
doi: 10.3389/fgene.2011.00100. eCollection 2011.

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

Mark Steven Miller  1 , Lance D Miller
Affiliations

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

Mark Steven Miller et al. Front Genet. .

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.

Keywords: cancer; mutation; ras; tumorigenesis.

PubMed Disclaimer

References

    1. Agbunag C., Bar-Sagi D. (2004). Oncogenic K-ras drives cell cycle progression and phenotypic conversion of primary pancreatic duct epithelial cells. Cancer Res. 64, 5659–566310.1158/0008-5472.CAN-04-0807 - DOI - PubMed
    1. Barbacid M. (1987). Ras genes. Annu. Rev. Biochem. 56, 779–82710.1146/annurev.bi.56.070187.004023 - DOI - PubMed
    1. Barbie D. A., Tamayo P., Boehm J. S., Kim S. Y., Moody S. E., Dunn I. F., Schinzel A. C., Sandy P., Meylan E., Scholl C., Frohling S., Chan E. M., Sos M. L., Michel K., Mermel C., Silver S. J., Weir B. A., Reiling J. H., Sheng Q., Gupta P. B., Wadlow R. C., Le H., Hoersch S., Wittner B. S., Ramaswamy S., Livingston D. M., Sabatini D. M., Meyerson M., Thomas R. K., Lander E. S., Mesirov J. P., Root D. E., Gilliland D. G., Jacks T., Hahn W. C. (2009). Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 462, 108–11210.1038/nature08460 - DOI - PMC - PubMed
    1. Beer D. G., Kardia S. L., Huang C. C., Giordano T. J., Levin A. M., Misek D. E., Lin L., Chen G., Gharib T. G., Thomas D. G., Lizyness M. L., Kuick R., Hayasaka S., Taylor J. M., Iannettoni M. D., Orringer M. B., Hanash S. (2002) Gene-expression profiles predict survival of patients with lung adenocarcinoma. Nat. Med. 8, 816–824 - PubMed
    1. Bhattacharjee A., Richards W. G., Staunton J., Li C., Monti S., Vasa P., Ladd C., Beheshti J., Bueno R., Gillette M., Loda M., Weber G., Mark E. J., Lander E. S., Wong W., Johnson B. E., Golub T. R., Sugarbaker D. J., Meyerson M. (2001). Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc. Natl. Acad. Sci. U.S.A. 98, 13790–1379510.1073/pnas.191502998 - DOI - PMC - PubMed

LinkOut - more resources