%0 Journal Article
%T Single Nucleotide Polymorphism Array Lesions, TET2, DNMT3A, ASXL1 and CBL Mutations Are Present in Systemic Mastocytosis
%A Fabiola Traina
%A Valeria Visconte
%A Anna M. Jankowska
%A Hideki Makishima
%A Christine L. O¡¯Keefe
%A Paul Elson
%A Yingchun Han
%A Fred H. Hsieh
%A Mikkael A. Sekeres
%A Raghuveer Singh Mali
%A Matt Kalaycio
%A Alan E. Lichtin
%A Anjali S. Advani
%A Hien K. Duong
%A Edward Copelan
%A Reuben Kapur
%A Sara T. Olalla Saad
%A Jaroslaw P. Maciejewski
%A Ramon V. Tiu
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0043090
%X 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.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0043090