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NRAS
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Interpretation 4
Tier 1
NRAS
Variants
NRAS any mutation
Primary Sites
Blood
Bone Marrow
Tumor Types
Acute Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Myelodysplastic Syndrome
B Lymphoblastic Leukemia/Lymphoma
Acute Leukemia of Unspecified Cell Type
Anemia, Unspecified
Atypical Chronic Myeloid Leukemia
Chronic Myeloid Leukemia
Chronic Neutrophilic Leukemia
Cytopenia
Eosinophilia
Essential Thrombocythemia
Histiocytic and Dendritic Cell Neoplasms
Langerhans Cell Histiocytosis
Leukocytosis
Leukopenia
Mast Cell Neoplasm
MDS with Ring Sideroblasts
Monocytosis
Myelodysplastic/Myeloproliferative Neoplasm
Myeloproliferative Neoplasm
Myeloid Neoplasm
Other Acute Leukemia
Polycythemia Vera
Polycythemia
Primary Myelofibrosis
T Lymphoblastic Leukemia/Lymphoma
Thrombocytopenia, Unspecified
Thrombocytosis
Interpretation

NRAS encodes a membrane protein GTPase that is a central mediator of downstream growth factor receptor signaling, critical for cell proliferation and survival. Mutations in codons 12, 13, and 61 of NRAS have been reported in 7-22% of acute myeloid leukemia, 12% of chronic myelomonocytic leukemia, 20% of blastic plasmacytoid dendritic cell neoplasm, 16% of juvenile myelomonocytic leukemia, 4-10% of myelodysplastic syndromes, and 5% of primary myelofibrosis. In addition, NRAS mutations have been described in approximately 15% of cases of B-ALL and, interestingly, some cases of ALL may show more than one abnormality in the RAS pathway. NRAS mutations are associated with an unfavorable prognosis in chronic myelomonocytic leukemia and primary myelofibrosis. NRAS mutations are also associated with an unfavorable prognosis in myelodysplastic syndrome, particularly in patients predicted to have lower-risk myelodysplastic syndrome (NCCN Guidelines for Myelodysplastic Syndromes). NRAS mutations do not seem to have significant prognostic impact in AML.

Citations
  1. Jain N, et al. Phase II study of the oral MEK inhibitor selumetinib in advanced acute myelogenous leukemia: a University of Chicago phase II consortium trial. Clin Cancer Res 2014;20(2):490-8
  2. Murphy DM, et al. NRAS mutations with low allele burden have independent prognostic significance for patients with lower risk myelodysplastic syndromes. Leukemia 2013;27(10):2077-81
  3. Bejar R, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med 2011;364(26):2496-506
  4. Bacher U, et al. A comparative study of molecular mutations in 381 patients with myelodysplastic syndrome and in 4130 patients with acute myeloid leukemia. Haematologica 2007;92(6):744-52
  5. Dicker F, et al. Mutation analysis for RUNX1, MLL-PTD, FLT3-ITD, NPM1 and NRAS in 269 patients with MDS or secondary AML. Leukemia 2010;24(8):1528-32
  6. Ricci C, et al. RAS mutations contribute to evolution of chronic myelomonocytic leukemia to the proliferative variant. Clin Cancer Res 2010;16(8):2246-56
  7. Tyner JW, et al. High-throughput sequencing screen reveals novel, transforming RAS mutations in myeloid leukemia patients. Blood 2009;113(8):1749-55
  8. Al-Kali A, et al. Prognostic impact of RAS mutations in patients with myelodysplastic syndrome. Am J Hematol 2013;88(5):365-9
  9. Zhang J, et al. Key pathways are frequently mutated in high-risk childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood 2011;118(11):3080-7
  10. Bacher U, et al. Implications of NRAS mutations in AML: a study of 2502 patients. Blood 2006;107(10):3847-53
  11. Metzeler KH, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood 2016;128(5):686-98
  12. Menezes J, et al. Exome sequencing reveals novel and recurrent mutations with clinical impact in blastic plasmacytoid dendritic cell neoplasm. Leukemia 2014;28(4):823-9
  13. Sakaguchi H, et al. Exome sequencing identifies secondary mutations of SETBP1 and JAK3 in juvenile myelomonocytic leukemia. Nat Genet 2013;45(8):937-41
  14. Elena C, et al. Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia. Blood 2016;128(10):1408-17
  15. Tenedini E, et al. Targeted cancer exome sequencing reveals recurrent mutations in myeloproliferative neoplasms. Leukemia 2014;28(5):1052-9
  16. Haferlach T, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia 2014;28(2):241-7
  17. Burgess MR, et al. Preclinical efficacy of MEK inhibition in Nras-mutant AML. Blood 2014;124(26):3947-55
Last updated: 2019-08-28 14:54:00 UTC
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