Nras

NRAS is an enzyme that is encoded by the NRAS gene in humans. NRAS was initially discovered in human neuroblastoma cells (NRAS = abbreviation for "Neuroblastoma RAS"). N-RAS oncogene is a member of the RAS gene family, which includes KRAS, HRAS and the inactive pseudogenes c-HRAS2, c-KRAS1 and c- N-RAS. The NRAS gene is located on chromosome 1.

NRAS has GTP/GDP binding and GTPase activity and functions as a G-like regulatory protein. The enzyme is involved in the normal control of cell growth. Activating mutations in the NRAS gene lead to a stabilization of NRAS in GTP-bound form. The GTP binding leads to a permanent activation of BRAF and PI3K (phosphoinositide 3-kinase). PI3K phosphorylates phosphatidylinositol to phosphatidylinositol triphosphate. PI3K regulates cell survival, proliferation and growth.

In oncology, the determination of NRAS mutation status is important in the treatment of patients with colon carcinoma and malignant melanoma, among others. NRAS mutations are also occasionally found in lung carcinoma (around 1%).

In melanoma , a mutated BRAF gene is detected in 40 to 50% of patients, a mutated NRAS gene in 15 to 20% and a mutated KIT gene in 2-5%. These mutations are usually exclusive, i.e. either a BRAF mutation, NRAS mutation or KIT mutation is found in a tumor.

2 BRAF inhibitors that inhibit the mutated BRAF are approved for the monotherapy of metastatic melanoma: vemurafenib and dabrafenib. These substances can achieve response rates of 50 to 60 % in BRAF-mutated patients, and median survival is extended to up to 20 months. However, the therapeutic success is often not permanent.

An NRAS mutation analysis can be performed on paraffin-embedded tumor material.

1. Held L et al (2011) Oncogenetics of melanoma: Basis for molecular diagnostics. J Dtsch Dermatol Ges 9:510-517
2. Marshall CJ et al (1982) A transforming gene present in human sarcoma cell lines. Nature 299: 171-173.
3. Shimizu K et al. (1983) Isolation and preliminary characterization of the transforming gene of a human neuroblastoma cell line. PNAS 80: 383-387.