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

Research output: Contribution to journalArticle

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Abstract

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
Article numbere43090
JournalPLoS One
Volume7
Issue number8
DOIs
StatePublished - Aug 15 2012

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Systemic Mastocytosis
Polymorphism
single nucleotide polymorphism
Single Nucleotide Polymorphism
Nucleotides
mutation
Mutation
Karyotyping
karyotyping
Survival
Genes
Uniparental Disomy
Mastocytosis
Defects
chromosome aberrations
Loss of Heterozygosity
Chromosome Aberrations
prognosis
heterozygosity
pathogenesis

ASJC Scopus subject areas

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

Cite this

Traina, F., Visconte, V., Jankowska, A. M., Makishima, H., O'Keefe, C. L., Elson, 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]. https://doi.org/10.1371/journal.pone.0043090

Single nucleotide polymorphism array lesions, TET2, DNMT3A, ASXL1 and CBL mutations are present in systemic mastocytosis. / Traina, Fabiola; Visconte, Valeria; Jankowska, Anna M.; Makishima, Hideki; O'Keefe, Christine L.; Elson, Paul; Han, Yingchun; Hsieh, Fred H.; Sekeres, Mikkael A.; Mali, Raghuveer Singh; Kalaycio, Matt; Lichtin, Alan E.; Advani, Anjali S.; Duong, Hien K.; Copelan, Edward; Kapur, Reuben; Olalla Saad, Sara T.; Maciejewski, Jaroslaw P.; Tiu, Ramon V.

In: PLoS One, Vol. 7, No. 8, e43090, 15.08.2012.

Research output: Contribution to journalArticle

Traina, F, Visconte, V, Jankowska, AM, Makishima, H, O'Keefe, CL, Elson, P, Han, Y, Hsieh, FH, Sekeres, MA, Mali, RS, Kalaycio, M, Lichtin, AE, Advani, AS, Duong, HK, Copelan, E, Kapur, R, Olalla Saad, ST, Maciejewski, JP & Tiu, RV 2012, 'Single nucleotide polymorphism array lesions, TET2, DNMT3A, ASXL1 and CBL mutations are present in systemic mastocytosis', PLoS One, vol. 7, no. 8, e43090. https://doi.org/10.1371/journal.pone.0043090
Traina, Fabiola ; Visconte, Valeria ; Jankowska, Anna M. ; Makishima, Hideki ; O'Keefe, Christine L. ; Elson, Paul ; Han, Yingchun ; Hsieh, Fred H. ; Sekeres, Mikkael A. ; Mali, Raghuveer Singh ; Kalaycio, Matt ; Lichtin, Alan E. ; Advani, Anjali S. ; Duong, Hien K. ; Copelan, Edward ; Kapur, Reuben ; Olalla Saad, Sara T. ; Maciejewski, Jaroslaw P. ; Tiu, Ramon V. / Single nucleotide polymorphism array lesions, TET2, DNMT3A, ASXL1 and CBL mutations are present in systemic mastocytosis. In: PLoS One. 2012 ; Vol. 7, No. 8.
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abstract = "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.",
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AU - Traina, Fabiola

AU - Visconte, Valeria

AU - Jankowska, Anna M.

AU - Makishima, Hideki

AU - O'Keefe, Christine L.

AU - Elson, Paul

AU - Han, Yingchun

AU - Hsieh, Fred H.

AU - Sekeres, Mikkael A.

AU - Mali, Raghuveer Singh

AU - Kalaycio, Matt

AU - Lichtin, Alan E.

AU - Advani, Anjali S.

AU - Duong, Hien K.

AU - Copelan, Edward

AU - Kapur, Reuben

AU - Olalla Saad, Sara T.

AU - Maciejewski, Jaroslaw P.

AU - Tiu, Ramon V.

PY - 2012/8/15

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N2 - 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.

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