Actions

NRAS

From www.haematologyetc.co.uk


Gene affected:
NRAS, the RAS gene originally identified from neuroblastoma cells hence N-RAS


Clinical significance
RAS mutations are frequent in all cancers, NRAS is particularly associated with myeloid disorders. Generally the mutations do not appear to carry an adverse (or favourable) prognosis, although occurrence in MDS may be associated with a worse outcome.



Function of gene

NRAS is a member of the RAS oncogene family originally isolated from neuroblastoma cells. Like all members of the Ras family proteins, the NRAS protein is a small GTP/GDP-linked signal proteins (i.e. it is activated when bound to GTP and inactive when GDP is bound) and may be viewed as an on/off switch associated with various signal pathways (particularly the RAF MEK ERK pathway). Activated signalling occurs in response to external stimuli to switch on RAS with downstream signal events that ultimately affect cell fate (proliferation or death). For this reason, mutation affecting RAS family members is very frequent in cancer of all types (probably 25% of cancers overall). NRAS is the most frequently mutated RAS-family member in haematological malignancies.


NGS panel gene coverage

Panel covers exons: 2,3,4


Occurrence:


Generally the most frequent RAS oncogenic mutation in haematology involve NRAS, with mutation of KRAS being less frequent and involvement by HRAS being rare.

CMML 19% (range 2-43)
AML 11% (range 10-44)
MDS 5% (range 4-9)


Associated genetic features:

Mutations affecting members of the RAS family generally do not occur together with other mutations simultaneously affecting cell-signal related proteins (BCR/ABL1 or FLT3). Also lesions affecting multiple RAS family members are rarely seen.


Links

GeneWiki link:
Gene Wiki entry for NRAS
References
1. Overview reference
2. NRAS prognosis AML (1)
3. RAS and prognosis in AML (2)
4. NRAS and prognosis in MDS
5. Impact in CMML
6. Relationship to cytogenetic features