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SRSF2
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Interpretation 64
Tier 1
SRSF2
Variants
SRSF2 codon(s) 95 missense
Primary Sites
Blood
Bone Marrow
Tumor Types
Chronic Myelomonocytic Leukemia
Myelodysplastic Syndrome
Acute Myeloid Leukemia
Primary Myelofibrosis
Acute Leukemia of Unspecified Cell Type
Anemia, Unspecified
Atypical Chronic Myeloid Leukemia
B Lymphoblastic Leukemia/Lymphoma
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
T Lymphoblastic Leukemia/Lymphoma
Thrombocytopenia, Unspecified
Thrombocytosis
Interpretation

SRSF2 is a member of the serine/arginine-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. It interacts with other spliceosomal components bound to both the 5- and 3-splice sites during spliceosome assembly. SRSF2 mutations typically occur as missense mutations at Pro95. SRSF2 mutations have been reported in approximately 40% of cases of chronic myelomonocytic leukemia, but they may not have prognostic significance in that entity. Comutation of TET2 and SRSF2 was highly predictive of a myeloid neoplasm characterized by myelodysplasia and monocytosis, including but not limited to, chronic myelomonocytic leukemia. In addition, SRSF2 mutations have been reported in approximately 15-20% of cases of myelodysplastic syndrome. SRSF2 mutations have also been described in 5-20% of patients with acute myeloid leukemia and appear to be enriched among AML patients with reduced blast counts. SRSF2 has been found to be mutated in approximately 10% of cases of primary myelofibrosis where mutations may occur together with mutations in JAK2, MPL, TET2, CBL, ASXL1, EZH2, IDH1/2. SRSF2 mutations are also present in 8% of blastic plasmacytoid dendritic cell neoplasm and 3% of polythemia vera. SRSF2 mutations tend to be (although are not entirely) exclusive of mutations in other splicing factor components. SRSF2 mutations are associated with a poor prognosis in myelodysplastic syndrome (NCCN Guidelines for Myelodysplastic Syndromes), primary myelofibrosis, polycythemia vera, and KIT D816V-mutated advanced systemic mastocytosis. SRSF2 mutations are also reported to be highly specific for secondary acute myeloid leukemia, and may also be helpful in identifying a subset of elderly patients with de novo acute myeloid leukemia and therapy-related AML with worse clinical outcomes.

Citations
  1. Guglielmelli P, et al. The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: an international study of 797 patients. Leukemia 2014;28(9):1804-10
  2. Vannucchi AM, et al. Mutations and prognosis in primary myelofibrosis. Leukemia 2013;27(9):1861-9
  3. Haferlach T, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia 2014;28(2):241-7
  4. Taskesen E, et al. Two splice-factor mutant leukemia subgroups uncovered at the boundaries of MDS and AML using combined gene expression and DNA-methylation profiling. Blood 2014;123(21):3327-35
  5. Patnaik MM, et al. Spliceosome mutations involving SRSF2, SF3B1, and U2AF35 in chronic myelomonocytic leukemia: prevalence, clinical correlates, and prognostic relevance. Am J Hematol 2013;88(3):201-6
  6. Thol F, et al. Frequency and prognostic impact of mutations in SRSF2, U2AF1, and ZRSR2 in patients with myelodysplastic syndromes. Blood 2012;119(15):3578-84
  7. 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
  8. Metzeler KH, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood 2016;128(5):686-98
  9. 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
  10. Tefferi A, et al. Targeted deep sequencing in polycythemia vera and essential thrombocythemia. Blood Adv 2016;1(1):21-30
  11. Jawhar M, et al. Additional mutations in SRSF2, ASXL1 and/or RUNX1 identify a high-risk group of patients with KIT D816V(+) advanced systemic mastocytosis. Leukemia 2016;30(1):136-43
  12. Malcovati L, et al. Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia. Blood 2014;124(9):1513-21
  13. Lindsley RC, et al. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood 2015;125(9):1367-76
Last updated: 2018-11-12 20:40:58 UTC
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