TY - JOUR
T1 - Myeloid neoplasms with isolated isochromosome 17q demonstrate a high frequency of mutations in SETBP1, SRSF2, ASXL1 and NRAS
AU - Kanagal Shamanna, Rashmi
AU - Luthra, Rajyalakshmi
AU - Yin, Cheng Cameron
AU - Patel, Keyur Pravinchandra
AU - Takahashi, Koichi
AU - Lu, Xinyan
AU - Lee, John
AU - Zhao, Chong
AU - Stingo, Francesco
AU - Zuo, Zhuang
AU - Routbort, Mark J
AU - Singh, Rajesh R.
AU - Fox, Patricia
AU - Ravandi-Kashani, Farhad
AU - Garcia-Manero, Guillermo
AU - Medeiros, L Jeffrey
AU - Bueso-Ramos, Carlos E
PY - 2016/3/22
Y1 - 2016/3/22
N2 - 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).
AB - 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).
KW - ASXL1
KW - Isochromosome 17q
KW - Myeloid neoplasms
KW - SETBP1
KW - SRSF2
UR - http://www.scopus.com/inward/record.url?scp=84971668341&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84971668341&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.7350
DO - 10.18632/oncotarget.7350
M3 - Article
C2 - 26883102
AN - SCOPUS:84971668341
SN - 1949-2553
VL - 7
SP - 14251
EP - 14258
JO - Oncotarget
JF - Oncotarget
IS - 12
ER -