vendredi 16 mars 2012

Mutated genes in cancer (58) – NRAS


In databases:

● Entrez ( 4893 or NRAS
● Ensembl ( ENSG00000213281
● UniProt ( P01111
● GeneCards ( NRAS
● HGNC ( 7989 or NRAS

Gene locus :


Protein name:

Neuroblastoma RAS viral (v-ras) oncogene homolog

Protein Size:

189 amino acids; about 21 kDa


NRAS is an oncogene encoding a membrane protein that shuttles between the Golgi apparatus and the plasma membrane. This shuttling is regulated through palmitoylation and depalmitoylation by the ZDHHC9-GOLGA7 complex. The encoded protein, which has intrinsic GTPase activity, is activated to a GTP-bound form by a GTPase activating protein and inactivated to a GDP-bound form by a guanine nucleotide-exchange factor.

Cancer-related alterations:

Genetic defects in NRAS are a cause of juvenile myelomonocytic leukemia (JMML). JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia.

Somatic mutations in a variety of tumors: skin, bile duct, thyroid, haematopoietic and lymphoid tissue, testis… Most mutation events are substitutions. Somatic mutation hot spots are observed at aminoacids 12, 13 and 61


As RAS is frequently mutated in human cancer, it has attracted significant attention as a target for anticancer therapy. Unfortunately, efforts to develop direct inhibitors of RAS have fallen short of expectations and no direct inhibitor of KRAS or NRAS has shown meaningful clinical activity to date. Alternative approaches include inhibitors of
the key downstream effectors of RAS.

References (open access):

Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations. Matsuda K, Shimada A, Yoshida N, Ogawa A, Watanabe A, Yajima S, Iizuka S, Koike K, Yanai F, Kawasaki K, Yanagimachi M, Kikuchi A, Ohtsuka Y, Hidaka E, Yamauchi K, Tanaka M, Yanagisawa R, Nakazawa Y, Shiohara M, Manabe A, Kojima S, Koike K. Blood. 2007 Jun 15;109(12):5477-80.

Childhood myelodysplastic syndrome: focus on the approach to diagnosis and treatment of juvenile myelomonocytic leukemia. Loh ML. Hematology Am Soc Hematol Educ Program. 2010;2010:357-62.

Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias. Rocquain J, Carbuccia N, Trouplin V, Raynaud S, Murati A, Nezri M, Tadrist Z, Olschwang S, Vey N, Birnbaum D, Gelsi-Boyer V, Mozziconacci MJ. BMC Cancer. 2010 Aug 2;10:401.


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