Significance of Genome-Wide Analysis of Copy Number Alterations and UPD in Myelodysplastic Syndromes using Combined CGH – SNP Arrays
Ausaf Ahmad and M. Anwar Iqbal
Affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave., Box 608 Rochester, NY 14642, USA.
Genetic information is an extremely valuable data source in characterizing the personal nature of cancer. Chromosome
instability is a hallmark of most cancer cells. Chromosomal abnormalities are correlated with poor prognosis, disease classification, risk
stratification, and treatment selection. Copy number alterations (CNAs) are an important molecular signature in cancer initiation,
development, and progression. Recent application of whole-genome tools to characterize normal and cancer genomes provides the
powerful molecular cytogenetic means to enumerate the multiple somatic, genetic and epigenetic alterations that occur in cancer.
Combined array comparative genomic hybridization (aCGH) with single nucleotide polymorphism (SNP) array is a useful technique
allowing detection of CNAs and loss of heterozygosity (LOH) or uni-parental disomy (UPD) together in a single experiment. It also
provides allelic information on deletions, duplications, and amplifications. UPD can result in an abnormal phenotype when the
chromosomes involved are imprinted. Myelodysplastic syndromes (MDS) are the most common clonal stem cell hematologic malignancy
characterized by ineffective hematopoiesis, which leads to rapid progression into acute myeloid leukemia. UPD that occurs without
concurrent changes in the gene copy number is a common chromosomal defect in hematologic malignancies, especially in MDS.
Approximately 40-50% of MDS patients do not have karyotypic abnormalities that are detectable using classical metaphase cytogenetic
techniques (MC) because of inherent limitations of MC, low resolution and the requirement of having dividing cells. In this review, we
highlight advances in the clinical application of microarray technology in MDS and discuss the clinical potential of microarray.
Keywords: Array comparative genomic hybridization, copy neutral genomic loss of heterozygosity, copy number aberrations,
myelodysplastic syndromes, single nucleotide polymorphism, and uni-parental disomy
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