title: Myeloid neoplasms with isolated isochromosome 17q demonstrate a high frequency of mutations in SETBP1, SRSF2, ASXL1 and NRAS.
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).
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Kanagal-Shamanna
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Cameron C
authors.initials: CC
authors.lastname: Yin
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Keyur P
authors.initials: KP
authors.lastname: Patel
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: John
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Chong
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Stingo
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Routbort
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Singh
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Fox
authors.affiliation: Department of Statistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.affiliation: Department of Statistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Bueso-Ramos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics*; D000068103:Serine-Arginine Splicing Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: C473949:ASXL1 protein, human; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C425066:SETBP1 protein, human; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
keywords: ASXL1; SETBP1; SRSF2; isochromosome 17q; myeloid neoplasms