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

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64 Scopus citations


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.

Original languageEnglish (US)
Article numbere43090
JournalPloS one
Issue number8
StatePublished - Aug 15 2012


ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Traina, F., Visconte, V., Jankowska, A. M., Makishima, H., O'Keefe, C. L., Elson, P., Han, Y., Hsieh, F. H., Sekeres, M. A., Mali, R. S., Kalaycio, M., Lichtin, A. E., Advani, A. S., Duong, H. K., Copelan, E., Kapur, R., Olalla Saad, S. T., Maciejewski, J. P., & Tiu, R. V. (2012). Single nucleotide polymorphism array lesions, TET2, DNMT3A, ASXL1 and CBL mutations are present in systemic mastocytosis. PloS one, 7(8), [e43090].