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ZRSR2
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Interpretation 78
Tier 1
ZRSR2
Variants
ZRSR2 any mutation
Primary Sites
Blood
Bone Marrow
Tumor Types
Myeloproliferative Neoplasm
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Chronic Myelomonocytic Leukemia
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
Myeloid Neoplasm
Other Acute Leukemia
Polycythemia Vera
Polycythemia
Primary Myelofibrosis
T Lymphoblastic Leukemia/Lymphoma
Thrombocytopenia, Unspecified
Thrombocytosis
Interpretation

ZRSR2 endoes a component of the RNA splicing machinery which associates with the U2 auxillary factor and is involved in the recognition of the 3'-splice site during the stages of spliceosome assembly. Mutations in ZRSR2 have been reported in approximately 3-11% of myelodysplasia, 4-8% of chronic myelomonocytic leukemia, 8% of blastic plasmacytoid dendritic cell neoplasm and less than 5% of acute myeloid leukemia and myeloproliferative neoplasms. Unlike other spliceosomal genes, ZRSR2 mutations do not occur in select "hot spots". Nearly all reported mutations are nonsense or frameshift mutations, compatible with loss-of-function mutations and suggesting a tumor suppressor role of ZRSR2. ZRSR2 mutations tend to be exclusive of mutations in most other components of the RNA splicing machinery. Aberrant splicing of U12-type introns has been shown to be a hallmark feature of MDS with ZRSR2 mutations. ZRSR2 mutations are associated with an unfavorable prognosis in myelodysplastic syndrome (NCCN Guidelines for Myelodysplastic Syndromes). ZRSR2 mutations are also reported to be highly specific for secondary acute myeloid leukemia, and may also be helpful in identifying a subset of therapy-related AML and elderly de novo AML with worse clinical outcomes.

Citations
  1. Yoshida K, et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 2011;478(7367):64-9
  2. Larsson CA, et al. The changing mutational landscape of acute myeloid leukemia and myelodysplastic syndrome. Mol Cancer Res 2013;11(8):815-27
  3. 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
  4. Damm F, et al. Mutations affecting mRNA splicing define distinct clinical phenotypes and correlate with patient outcome in myelodysplastic syndromes. Blood 2012;119(14):3211-8
  5. Haferlach T, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia 2014;28(2):241-7
  6. 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
  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. Lindsley RC, et al. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood 2015;125(9):1367-76
  10. Madan V, et al. Aberrant splicing of U12-type introns is the hallmark of ZRSR2 mutant myelodysplastic syndrome. Nat Commun 2015;6():6042
Last updated: 2019-08-28 14:54:02 UTC
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