High-Resolution Genomic Arrays Facilitate Detection of Novel Cryptic Chromosomal Lesions in Myelodysplastic Syndromes

Christine L. O'Keefe, Ramon Tiu, Lukasz Gondek, Jennifer Powers, Karl S. Theil, Matt Kalaycio, Alan Lichtin, Mikkael A. Sekeres, Jaroslaw P. Maciejewski

Research output: Contribution to journalArticle

Abstract

Objective: Unbalanced chromosomal aberrations are common in myelodysplastic syndromes and have prognostic implications. An increased frequency of cytogenetic changes may reflect an inherent chromosomal instability due to failure of DNA repair. Therefore, it is likely that chromosomal defects in myelodysplastic syndromes may be more frequent than predicted by metaphase cytogenetics and new cryptic lesions may be revealed by precise analysis methods. Methods: We used a novel high-resolution karyotyping technique, array-based comparative genomic hybridization, to investigate the frequency of cryptic chromosomal lesions in a cohort of 38 well-characterized myelodysplastic syndromes patients; results were confirmed by microsatellite quantitative PCR or single nucleotide polymorphism analysis. Results: As compared to metaphase karyotyping, chromosomal abnormalities detected by array-based analysis were encountered more frequently and in a higher proportion of patients. For example, chromosomal defects were found in patients with a normal karyotype by traditional cytogenetics. In addition to verifying common abnormalities, previously cryptic defects were found in new regions of the genome. Cryptic changes often overlapped chromosomes and regions frequently identified as abnormal by metaphase cytogenetics. Conclusion: The results underscore the instability of the myelodysplastic syndromes genome and highlight the utility of array-based karyotyping to study cryptic chromosomal changes which may provide new diagnostic information.

Original languageEnglish (US)
Pages (from-to)240-251
Number of pages12
JournalExperimental Hematology
Volume35
Issue number2
DOIs
StatePublished - Feb 2007
Externally publishedYes

Fingerprint

Myelodysplastic Syndromes
Cytogenetics
Karyotyping
Metaphase
Chromosome Aberrations
Genome
Chromosomal Instability
Comparative Genomic Hybridization
Karyotype
DNA Repair
Microsatellite Repeats
Single Nucleotide Polymorphism
Chromosomes
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

High-Resolution Genomic Arrays Facilitate Detection of Novel Cryptic Chromosomal Lesions in Myelodysplastic Syndromes. / O'Keefe, Christine L.; Tiu, Ramon; Gondek, Lukasz; Powers, Jennifer; Theil, Karl S.; Kalaycio, Matt; Lichtin, Alan; Sekeres, Mikkael A.; Maciejewski, Jaroslaw P.

In: Experimental Hematology, Vol. 35, No. 2, 02.2007, p. 240-251.

Research output: Contribution to journalArticle

O'Keefe, CL, Tiu, R, Gondek, L, Powers, J, Theil, KS, Kalaycio, M, Lichtin, A, Sekeres, MA & Maciejewski, JP 2007, 'High-Resolution Genomic Arrays Facilitate Detection of Novel Cryptic Chromosomal Lesions in Myelodysplastic Syndromes', Experimental Hematology, vol. 35, no. 2, pp. 240-251. https://doi.org/10.1016/j.exphem.2006.09.016
O'Keefe, Christine L. ; Tiu, Ramon ; Gondek, Lukasz ; Powers, Jennifer ; Theil, Karl S. ; Kalaycio, Matt ; Lichtin, Alan ; Sekeres, Mikkael A. ; Maciejewski, Jaroslaw P. / High-Resolution Genomic Arrays Facilitate Detection of Novel Cryptic Chromosomal Lesions in Myelodysplastic Syndromes. In: Experimental Hematology. 2007 ; Vol. 35, No. 2. pp. 240-251.
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