title: Genomic array as compared to karyotyping in myelodysplastic syndromes in a prospective clinical trial.
abstract: Karyotyping is considered as the gold standard in the genetic subclassification of myelodysplastic syndrome (MDS). Oligo/SNP-based genomic array profiling is a high-resolution tool that also enables genome wide analysis. We compared karyotyping with oligo/SNP-based array profiling in 104 MDS patients from the HOVON-89 study. Oligo/SNP-array identified all cytogenetically defined genomic lesions, except for subclones in two cases and balanced translocations in three cases. Conversely, oligo/SNP-based genomic array profiling had a higher success rate, showing 55 abnormal cases, while an abnormal karyotype was found in only 35 patients. In nine patients whose karyotyping was unsuccessful because of insufficient metaphases or failure, oligo/SNP-based array analysis was successful. Based on cytogenetic visible abnormalities as identified by oligo/SNP-based genomic array prognostic scores based on IPSS/-R were assigned. These prognostic scores were identical to the IPSS/-R scores as obtained with karyotyping in 95%-96% of the patients. In addition to the detection of cytogenetically defined lesions, oligo/SNP-based genomic profiling identified focal copy number abnormalities or regions of copy neutral loss of heterozygosity that were out of the scope of karyotyping and fluorescence in situ hybridization. Of interest, in 26 patients we demonstrated such cytogenetic invisible abnormalities. These abnormalities often involved regions that are recurrently affected in hematological malignancies, and may therefore be of clinical relevance. Our findings indicate that oligo/SNP-based genomic array can be used to identify the vast majority of recurrent cytogenetic abnormalities in MDS. Furthermore, oligo/SNP-based array profiling yields additional genetic abnormalities that may be of clinical importance.
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Marian J
authors.identifier: 0000-0002-9196-7430
authors.initials: MJ
authors.lastname: Stevens-Kroef
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Daniel
authors.initials: D
authors.lastname: Olde Weghuis
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Najat
authors.initials: N
authors.lastname: ElIdrissi-Zaynoun
authors.affiliation: Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Bert
authors.initials: B
authors.lastname: van der Reijden
authors.affiliation: Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Eline M P
authors.initials: EMP
authors.lastname: Cremers
authors.affiliation: Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Canan
authors.initials: C
authors.lastname: Alhan
authors.affiliation: Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Theresia M
authors.initials: TM
authors.lastname: Westers
authors.affiliation: Department of Hematology, Erasmus MC Cancer Institute, HOVON Data Center, Erasmus University Medical Center-Daniel den Hoed, Rotterdam, The Netherlands.
authors.forename: Heleen A
authors.initials: HA
authors.lastname: Visser-Wisselaar
authors.affiliation: Department of Hematology, Erasmus MC Cancer Institute, HOVON Data Center, Erasmus University Medical Center-Daniel den Hoed, Rotterdam, The Netherlands.
authors.forename: Dana A
authors.initials: DA
authors.lastname: Chitu
authors.affiliation: Department of Hematology, Erasmus MC Cancer Institute, HOVON Data Center, Erasmus University Medical Center-Daniel den Hoed, Rotterdam, The Netherlands.
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Cunha
authors.affiliation: Department of Experimental Hematology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
authors.affiliation: Department of Internal Medicine, Meander Medisch Centrum, Amersfoort, The Netherlands.
authors.forename: Saskia K
authors.initials: SK
authors.lastname: Klein
authors.affiliation: Department of Internal Medicine, Haga Ziekenhuis, The Hague, The Netherlands.
authors.forename: Pierre
authors.initials: P
authors.lastname: Wijermans
authors.affiliation: Department of Hematology, Erasmus University Medical Center-Daniel den Hoed, Rotterdam, The Netherlands.
authors.forename: Georgine E
authors.initials: GE
authors.lastname: de Greef
authors.affiliation: Department of Internal Medicine, Medisch Centrum Twente, Enschede, The Netherlands.
authors.forename: M Ron
authors.initials: MR
authors.lastname: Schaafsma
authors.affiliation: Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Muus
authors.affiliation: Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.affiliation: Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Arjan A
authors.initials: AA
authors.lastname: van de Loosdrecht
authors.affiliation: Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Joop H
authors.initials: JH
authors.lastname: Jansen
mesh_terms: D059786:Abnormal Karyotype; D006801:Humans; D007621:Karyotyping / Q000706:statistics & numerical data*; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000706:statistics & numerical data*; D011237:Predictive Value of Tests; D011446:Prospective Studies