Research Papers:

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 and Carlos E. Bueso-Ramos

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Oncotarget. 2016; 7:14251-14258. https://doi.org/10.18632/oncotarget.7350

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Rashmi Kanagal-Shamanna1, Rajyalakshmi Luthra1, Cameron C. Yin1, Keyur P. Patel1, Koichi Takahashi2, Xinyan Lu1, John Lee1, Chong Zhao1, Francesco Stingo2, Zhuang Zuo1, Mark J. Routbort1, Rajesh R. Singh1, Patricia Fox2, Farhad Ravandi3, Guillermo Garcia-Manero3, L. Jeffrey Medeiros1, Carlos E. Bueso-Ramos1

1Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

2Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

3Department of Statistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence to:

Rashmi Kanagal-Shamanna, e-mail: [email protected]

Carlos E. Bueso-Ramos, e-mail: [email protected]

Keywords: myeloid neoplasms, isochromosome 17q, SETBP1, SRSF2, ASXL1

Received: December 17, 2015     Accepted: January 29, 2016     Published: February 12, 2016


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).

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