title: Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
abstract: Single nucleotide polymorphism arrays (SNP-As) have emerged as an important tool in the identification of chromosomal defects undetected by metaphase cytogenetics (MC) in hematologic cancers, offering superior resolution of unbalanced chromosomal defects and acquired copy-neutral loss of heterozygosity. Myelodysplastic syndromes (MDSs) and related cancers share recurrent chromosomal defects and molecular lesions that predict outcomes. We hypothesized that combining SNP-A and MC could improve diagnosis/prognosis and further the molecular characterization of myeloid malignancies. We analyzed MC/SNP-A results from 430 patients (MDS = 250, MDS/myeloproliferative overlap neoplasm = 95, acute myeloid leukemia from MDS = 85). The frequency and clinical significance of genomic aberrations was compared between MC and MC plus SNP-A. Combined MC/SNP-A karyotyping lead to higher diagnostic yield of chromosomal defects (74% vs 44%, P < .0001), compared with MC alone, often through detection of novel lesions in patients with normal/noninformative (54%) and abnormal (62%) MC results. Newly detected SNP-A defects contributed to poorer prognosis for patients stratified by current morphologic and clinical risk schemes. The presence and number of new SNP-A detected lesions are independent predictors of overall and event-free survival. The significant diagnostic and prognostic contributions of SNP-A-detected defects in MDS and related diseases underscore the utility of SNP-A when combined with MC in hematologic malignancies.
authors.affiliation: Department of Translational Hematology and Oncology Research, Taussig Cancer Institute Center, Cleveland, OH, USA.
authors.forename: Ramon V
authors.initials: RV
authors.lastname: Tiu
authors.forename: Lukasz P
authors.initials: LP
authors.lastname: Gondek
authors.forename: Christine L
authors.initials: CL
authors.lastname: O'Keefe
authors.forename: Paul
authors.initials: P
authors.lastname: Elson
authors.forename: Jungwon
authors.initials: J
authors.lastname: Huh
authors.forename: Azim
authors.initials: A
authors.lastname: Mohamedali
authors.forename: Austin
authors.initials: A
authors.lastname: Kulasekararaj
authors.forename: Anjali S
authors.initials: AS
authors.lastname: Advani
authors.forename: Ronald
authors.initials: R
authors.lastname: Paquette
authors.forename: Alan F
authors.initials: AF
authors.lastname: List
authors.forename: Mikkael A
authors.initials: MA
authors.lastname: Sekeres
authors.forename: Michael A
authors.initials: MA
authors.lastname: McDevitt
authors.forename: Ghulam J
authors.initials: GJ
authors.lastname: Mufti
authors.forename: Jaroslaw P
authors.initials: JP
authors.lastname: Maciejewski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations / Q000706:statistics & numerical data; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D055815:Young Adult