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KRAS
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Interpretation 50
Tier 2
KRAS
Variants
KRAS codon(s) 12, 13, 61, 117, 146 any
Primary Sites
Blood
Bone Marrow
Tumor Types
Acute Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Myelodysplastic Syndrome
B Lymphoblastic Leukemia/Lymphoma
T 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
Thrombocytopenia, Unspecified
Thrombocytosis
Interpretation

KRAS is a well known proto-oncogene that belongs to the small GTPase family and functions as a central mediator of downstream growth factor receptor signaling, with a critical role for cell proliferation and survival. Pathogenic mutations in KRAS typically occur in codons 12-13 of exon 2 and codon 61 of exon 3; however, other, non-canonical, pathogenic mutations in KRAS have also been reported in acute myeoid leukemia. KRAS mutations have been described in approximately 3-15% of acute myeloid leukemia, 8-20% of chronic myelomonocytic leukemia, 14% of juvenile myelomonocytic leukemia, 8% of blastic plasmacytoid dendritic cell neoplasm 4% of patients with myelodysplastic syndrome, 2% of primary myelofibrosis, 12% of B cell acute lymphoblastic leukemia (often associated with MLL rearrangement) and 1-2% of T cell acute lymphoblastic leukemia. Investigation into the targetability of this pathway in leukemia has been attempted in some disease models.

Citations
  1. Trinquand A, et al. Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study. J Clin Oncol 2013;31(34):4333-42
  2. Park MJ, et al. Frequency of KRAS mutations in adult Korean patients with acute myeloid leukemia. Int J Hematol 2013;98(5):549-57
  3. Itzykson R, et al. Prognostic score including gene mutations in chronic myelomonocytic leukemia. J Clin Oncol 2013;31(19):2428-36
  4. Tyner JW, et al. High-throughput sequencing screen reveals novel, transforming RAS mutations in myeloid leukemia patients. Blood 2009;113(8):1749-55
  5. Liang DC, et al. K-Ras mutations and N-Ras mutations in childhood acute leukemias with or without mixed-lineage leukemia gene rearrangements. Cancer 2006;106(4):950-6
  6. Al-Kali A, et al. Prognostic impact of RAS mutations in patients with myelodysplastic syndrome. Am J Hematol 2013;88(5):365-9
  7. Gritsman K, et al. Hematopoiesis and RAS-driven myeloid leukemia differentially require PI3K isoform p110a. J Clin Invest 2014;124(4):1794-809
  8. Sakaguchi H, et al. Exome sequencing identifies secondary mutations of SETBP1 and JAK3 in juvenile myelomonocytic leukemia. Nat Genet 2013;45(8):937-41
  9. 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
  10. 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
  11. Metzeler KH, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood 2016;128(5):686-98
  12. Haferlach T, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia 2014;28(2):241-7
  13. Tenedini E, et al. Targeted cancer exome sequencing reveals recurrent mutations in myeloproliferative neoplasms. Leukemia 2014;28(5):1052-9
Last updated: 2018-11-12 20:40:39 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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