title: Characterization of chromosome arm 20q abnormalities in myeloid malignancies using genome-wide single nucleotide polymorphism array analysis.
abstract: Deletion of the long arm of chromosome 20 is a common abnormality associated with myeloid malignancies. We characterized abnormalities of chromosome 20 as defined by metaphase cytogenetics (MC) in patients with myeloid neoplasms to define commonly deleted regions (CDR) and commonly retained regions (CRR) using genome-wide, high resolution single nucleotide polymorphism array (SNP-A) analysis. We reviewed the MC results of a cohort of 1,162 patients with myeloid malignancies, including myelodysplastic syndromes (MDS), MDS/myeloproliferative neoplasia (MDS/MPN), and acute myeloid leukemia (AML). We further analyzed a subcohort of 532 patients by SNP-A using the Affymetrix Genome-Wide Human SNP Array 6.0 and GeneChip Human Mapping 250K Nsp arrays. By MC, 5% (54/1,162) harbored a deletion of 20q; in 30% (16/54), del(20q) was the sole cytogenetic abnormality. By SNP-A analysis, we identified del(20q) in 23 patients, 3 not detected by MC. In four cases, monosomy 20 with a marker chromosome by MC was proven to be an interstitial deletion of 20q by SNP-A. We defined 2 CDR and 2 CRR on chromosome arm 20q: CDR1 spanned 2.5 Mb between bands 20q11.23 and 20q12, while CDR2 encompassed 1.8 Mb within 20q13.12. CRR1 spanned 1.9 Mb within 20q11.21 and CRR2 encompassed 2.5 Mb within 20q13.33. In contrast to other chromosomes frequently affected by deletions, no somatic copy neutral loss of heterozygosity (CN-LOH) was detected. Our data suggest that SNP-A is useful for the detection of cryptic aberrations of chromosome 20q and allows for a more precise characterization of complex karyotypes. Furthermore, SNP-A allowed definition of a CDR on 20q.
authors.affiliation: Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Jungwon
authors.initials: J
authors.lastname: Huh
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: Monika
authors.initials: M
authors.lastname: Jasek
authors.forename: Hideki
authors.initials: H
authors.lastname: Makishima
authors.forename: Ania M
authors.initials: AM
authors.lastname: Jankowska
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.forename: Amit
authors.initials: A
authors.lastname: Verma
authors.forename: Karl S
authors.initials: KS
authors.lastname: Theil
authors.forename: Michael A
authors.initials: MA
authors.lastname: McDevitt
authors.forename: Jaroslaw P
authors.initials: JP
authors.lastname: Maciejewski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002890:Chromosomes, Human, Pair 20; D015331:Cohort Studies; D020732:Cytogenetic Analysis; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020641:Polymorphism, Single Nucleotide