NRAS mutations are rare in colorectal cancer.
Activating mutations in members of the RAS oncogene family (KRAS, HRAS, and NRAS) have been found in a variety of human malignancies, suggesting a dominant role in carcinogenesis. In colon cancers, KRAS mutations are common and clearly contribute to malignant progression. The frequency of NRAS mutations and their relationship with clinical, pathologic, and molecular features remains uncertain. We developed and validated a Pyroseqencing assay to detect NRAS mutations at codons 12, 13, and 61. Using a collection of 225 colorectal cancers from 2 prospective cohort studies, we examined the relationship between NRAS mutations, clinical outcome, and other molecular features, including mutation of KRAS, BRAF, and PIK3CA, microsatellite instability, and the CpG island methylator phenotype. Finally, we examined whether NRAS mutation was associated with patient survival or prognosis. NRAS mutations were detected in 5 (2.2%) of the 225 colorectal cancers and tended to occur in left-sided cancers arising in women, but did not seem to be associated with any of the molecular features that were examined.
Irahara
Natsumi
N
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Baba
Yoshifumi
Y
Nosho
Katsuhiko
K
Shima
Kaori
K
Yan
Liying
L
Dias-Santagata
Dora
D
Iafrate
Anthony John
AJ
Fuchs
Charles S
CS
Haigis
Kevin M
KM
Ogino
Shuji
S
D000368:Aged; D058534:Class I Phosphatidylinositol 3-Kinases; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D015257:DNA-Cytosine Methylases / Q000378:metabolism; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D057089:Pathology, Molecular / Q000379:methods; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods
C081573:DNA modification methylase SssI; D015257:DNA-Cytosine Methylases; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf