How do somatic mutations in patients with MDS relate to clinical features, considering the common occurrence of inactivating mutations in PcG genes like EZH2?
['["Loss-of-function mutations of EZH2, a catalytic component of polycomb repressive complex 2 (PRC2), are observed in ~\\\\n10% of patients with myelodysplastic syndrome (MDS), but are rare in acute myeloid leukaemia (AML)", "We describe the use of an oligo-SNP array for genomic profiling of aCNA and cnLOH, together with sequence analysis of recurrently mutated genes, in a patient with myelodysplastic syndrome (MDS) presenting with normal karyotype and FISH result", " Conditionally deleting Ezh2 in mature T cells dramatically reduced the production of BM-destructive Th1 cells in vivo, decreased BM-infiltrating Th1 cells, and rescued mice from BM failure.", "Acquired aplastic anemia (AA) is a potentially fatal bone marrow (BM) failure syndrome", "Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap.", "EZH2 mutations that cause Weaver syndrome are primarily missense variants and the rare truncating mutations reported to date are in the last exon, suggesting that simple haploinsufficiency is unlikely to be generating the overgrowth phenotype although the exact mechanism has not yet been determined", "Weaver syndrome and EZH2 mutations", "In 2011, mutations in the histone methyltransferase, EZH2, were shown to cause Weaver syndrome", "The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes. ", "Mutations in EZH2 cause Weaver syndrome", "These data show that mutations in EZH2 cause Weaver syndrome", "The EZH2 mutation spectrum in Weaver syndrome shows considerable overlap with the inactivating somatic EZH2 mutations recently reported in myeloid malignancies", "EZH2 mutations as the cause of Weaver syndrome and provide further links between histone modifications and regulation of human growth.", "Mutations at tyrosine 641 (Y641F, Y641N, Y641S and Y641H) in the SET domain of EZH2 have been identified in patients with certain subtypes of non-Hodgkin lymphoma (NHL)", "The EZH2 gene was previously reported to be located on chromosome 21q22 and was proposed as a candidate gene for some characteristics of the Down syndrome phenotype", "Recent extensive mutation analyses of the myeloid malignancies have revealed that inactivating somatic mutations in PcG genes such as EZH2 and ASXL1 occur frequently in patients with myelodysplastic disorders including myelodysplastic syndromes (MDSs) and MDS/myeloproliferative neoplasm (MPN) overlap disorders (MDS/MPN).", "EZH2 is frequently overexpressed and considered to be an oncogene in cancers; nevertheless, EZH2 is considered as a candidate tumor suppressor gene in MDS due to EZH2 mutations associated with poor survival.", "In 2011, mutations in the histone methyltransferase, EZH2, were shown to cause Weaver syndrome.", "Among them, Sotos and Weaver syndromes are clinically well defined and due to heterozygous mutations in NSD1 and EZH2, respectively.", "Weaver syndrome and EZH2 mutations: Clarifying the clinical phenotype.", "Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap.", "The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes.", "We postulated that mutations in writers of these two chromatin marks could cause overgrowth conditions, resembling Sotos or Weaver syndromes, in patients with no NSD1 or EZH2 abnormalities.", "Recent extensive mutation analyses of the myeloid malignancies have revealed that inactivating somatic mutations in PcG genes such as EZH2 and ASXL1 occur frequently in patients with myelodysplastic disorders including myelodysplastic syndromes (MDSs) and MDS/myeloproliferative neoplasm (MPN) overlap disorders (MDS/MPN). ", "Somatic mutations of epigenetic gene regulators are common in patients with myelodysplastic syndromes (MDS) and correlate with some clinical and laboratory features. ", "Recently, the advent of next generation sequencing (NGS) techniques has helped identify somatic gene mutations in 75-']
Somatic mutations of epigenetic gene regulators are common in patients with myelodysplastic syndromes (MDS) and correlate with some clinical and laboratory features. Recent extensive mutation analyses of the myeloid malignancies have revealed that inactivating somatic mutations in PcG genes such as EZH2 occur frequently in patients with myelodysplastic disorders including myelodysplastic syndromes (MDSs) and MDS/myeloproliferative neoplasm (MPN) overlap disorders (MDS/MPN). EZH2 mutations are associated with poor survival in MDS.
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