Myeloid neoplasms with isolated isochromosome 17q demonstrate a high frequency of mutations in SETBP1, SRSF2, ASXL1 and NRAS

Rashmi Kanagal-Shamanna*, Rajyalakshmi Luthra, Cameron C. Yin, Keyur P. Patel, Koichi Takahashi, Xinyan Lu, John Lee, Chong Zhao, Francesco Stingo, Zhuang Zuo, Mark J. Routbort, Rajesh R. Singh, Patricia Fox, Farhad Ravandi, Guillermo Garcia-Manero, L. Jeffrey Medeiros, Carlos E. Bueso-Ramos

*Corresponding author for this work

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Isolated isochromosome 17q, i(17q), accounts for less than 1% of myeloid neoplasms that are commonly classified as myelodysplastic/myeloproliferative neoplasms, acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN). We have shown previously that these cases have distinctive clinicopathologic features, a poor prognosis and absence of TP53 mutations. However, their molecular mutation profile has not been studied. Here, we explored the mutation profile of 32 cases of myeloid neoplasm with isolated i(17q) that included AML, MDS/MPN, MDS and MPN. In addition to the common i(17q), these neoplasms had frequent mutations in SRSF2 (55%), SETBP1 (59%), ASXL1 (55%), and NRAS (31%); TET2 and TP53 mutations were rare. Eight of 28 patients (29%) showed concurrent mutations in ASXL1, SRSF2, SETBP1 and RAS. There was a significant association between mutations in SETBP1 and RAS (p = 0.003). The mutation pattern was independent of the morphologic diagnosis. Sequential analysis of 5 cases showed evolution from a diploid karyotype to i(17q) and that SRSF2 and ASXL1 mutations precede the detection of i(17q) whereas SETBP1 mutations are associated with i(17q).

Original languageEnglish (US)
Pages (from-to)14251-14258
Number of pages8
JournalOncotarget
Volume7
Issue number12
DOIs
StatePublished - Mar 22 2016

Keywords

  • ASXL1
  • Isochromosome 17q
  • Myeloid neoplasms
  • SETBP1
  • SRSF2

ASJC Scopus subject areas

  • Oncology

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    Kanagal-Shamanna, R., Luthra, R., Yin, C. C., Patel, K. P., Takahashi, K., Lu, X., Lee, J., Zhao, C., Stingo, F., Zuo, Z., Routbort, M. J., Singh, R. R., Fox, P., Ravandi, F., Garcia-Manero, G., Jeffrey Medeiros, L., & Bueso-Ramos, C. E. (2016). Myeloid neoplasms with isolated isochromosome 17q demonstrate a high frequency of mutations in SETBP1, SRSF2, ASXL1 and NRAS. Oncotarget, 7(12), 14251-14258. https://doi.org/10.18632/oncotarget.7350