PLoS ONE (Jan 2012)

Single nucleotide polymorphism array lesions, TET2, DNMT3A, ASXL1 and CBL mutations are present in systemic mastocytosis.

  • Fabiola Traina,
  • Valeria Visconte,
  • Anna M Jankowska,
  • Hideki Makishima,
  • Christine L O'Keefe,
  • Paul Elson,
  • Yingchun Han,
  • Fred H Hsieh,
  • Mikkael A Sekeres,
  • Raghuveer Singh Mali,
  • Matt Kalaycio,
  • Alan E Lichtin,
  • Anjali S Advani,
  • Hien K Duong,
  • Edward Copelan,
  • Reuben Kapur,
  • Sara T Olalla Saad,
  • Jaroslaw P Maciejewski,
  • Ramon V Tiu

DOI
https://doi.org/10.1371/journal.pone.0043090
Journal volume & issue
Vol. 7, no. 8
p. e43090

Abstract

Read online

We hypothesized that analysis of single nucleotide polymorphism arrays (SNP-A) and new molecular defects may provide new insight in the pathogenesis of systemic mastocytosis (SM). SNP-A karyotyping was applied to identify recurrent areas of loss of heterozygosity and bidirectional sequencing was performed to evaluate the mutational status of TET2, DNMT3A, ASXL1, EZH2, IDH1/IDH2 and the CBL gene family. Overall survival (OS) was analyzed using the Kaplan-Meier method. We studied a total of 26 patients with SM. In 67% of SM patients, SNP-A karyotyping showed new chromosomal abnormalities including uniparental disomy of 4q and 2p spanning TET2/KIT and DNMT3A. Mutations in TET2, DNMT3A, ASXL1 and CBL were found in 23%, 12%, 12%, and 4% of SM patients, respectively. No mutations were observed in EZH2 and IDH1/IDH2. Significant differences in OS were observed for SM mutated patients grouped based on the presence of combined TET2/DNMT3A/ASXL1 mutations independent of KIT (P = 0.04) and sole TET2 mutations (P<0.001). In conclusion, TET2, DNMT3A and ASXL1 mutations are also present in mastocytosis and these mutations may affect prognosis, as demonstrated by worse OS in mutated patients.