RAS (rat sarcoma) gene

«The word RAS comes from a contraction of Rat sarcoma, the tumor where the first gene of the family was identified, as part of the genome of a retrovirus isolated from a carcinogenesis protocol [3].» It is «a family of genes that make proteins involved in cell signaling pathways (cellular signal transduction [2]) that control cell growth and cell death [1].» «RAS is a guanosine-nucleotide-binding protein. Specifically, it is a single-subunit small GTPase [2]». «When RAS is switched on by incoming signals, it subsequently switches on other proteins, which ultimately turn on genes involved in cell growth, differentiation, and survival. (...). RAS-regulated signal pathways control such processes as actin cytoskeletal integrity, cell proliferation, cell differentiation, cell adhesion, apoptosis, and cell migration [2].» «Mutated (changed) forms of the RAS gene may be found in some types of cancer. These changes may cause cancer cells to grow and spread in the body [1].» «Mutations in RAS genes can lead to the production of permanently activated RAS proteins. As a result, this can cause unintended and overactive signaling inside the cell, even in the absence of incoming signals. (...). The 3 RAS genes in humans (HRAS, KRAS, and NRAS) are the most common oncogenes in human cancer; mutations that permanently activate RAS are found in 20% to 25% of all human tumors and up to 90% in certain types of cancer (e.g., pancreatic cancer). For this reason, RAS inhibitors are being studied as a treatment for cancer and other diseases with RAS overexpression [2].»

«HRAS was initially isolated from the Harvey sarcoma virus. KRAS from the Kirsten sarcoma virus and NRAS was isolated by DNA [deoxyribonucleic acid]-mediated gene transfer from a human neuroblastoma cell line [3].»

«RAS gene mutations are among the most frequently mutated genes in human cancers, found in approximately 30% of all tumor types and in approximately 50% of colorectal cancer (CRC). (...). In addition, oncogenic RAS mutations cause acquired resistance to anti-epidermal growth factor receptor (EGFR) therapies such as cetuximab and panitumumab. Given its clinical relevance as an important predictive biomarker, the American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines recommend RAS testing for KRAS and NRAS mutations in exon 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146) when managing patients with metastatic colorectal cancer. [4].»

Bibliographic references:

[1] National Cancer Institute. (n.d.). NCI Dictionary of Cancer Terms. [online] Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/ras-gene-family [Accessed 28 Mar. 2019].

[2] En.wikipedia.org. (2019). Ras subfamily. [online] Available at: https://en.wikipedia.org/wiki/Ras_subfamily [Accessed 28 Mar. 2019].

[3] Pellicer A. (2011) RAS Genes. In: Schwab M. (eds) Encyclopedia of Cancer. Springer, Berlin, Heidelberg. Available at: https://doi.org/10.1007/978-3-642-16483-5_4951.

[4] Scott AJ, et al. Therapeutic Approaches to RAS Mutation. Cancer J. 2016 May-Jun; 22(3): 165–174. Available at: https://dx.doi.org/10.1097/PPO.0000000000000187.