Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics

• Published in: Leukemia Vol. 23; no. 9; pp. 1605 - 1613
• Main Authors: Heinrichs, S, Kulkarni, R V, Bueso-Ramos, C E, Levine, R L, Loh, M L, Li, C, Neuberg, D, Kornblau, S M, Issa, J-P, Gilliland, D G, Garcia-Manero, G, Kantarjian, H M, Estey, E H, Look, A T
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2009; Nature Publishing Group
• Subjects: Abnormalities; Adult; Aged; Aged, 80 and over; Arrays; Biological and medical sciences; Bone marrow; Cancer Research; Care and treatment; CD34 antigen; Chromosome 7; Chromosome Deletion; Copy number; Critical Care Medicine; Cytogenetics; Deoxyribonucleic acid; Disorders; DNA; Female; Genetic aspects; Genomics; Hematologic and hematopoietic diseases; Hematology; Heterozygosity; Humans; Intensive; Internal Medicine; Karyotypes; Karyotyping; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Loss of Heterozygosity; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - genetics; Nucleotides; Oligonucleotide Array Sequence Analysis; Oncology; original-article; Patients; Polymorphism; Polymorphism, Single Nucleotide; Risk factors; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Underpotential deposition; Uniparental Disomy; United States; myelodysplastic syndrome; SNP array; uniparental disomy; Chromosomal aberration; Uniparental disomy; Hematology; Cytogenetics; Deletion; Malignant hemopathy; Diagnosis; Myelodysplastic syndrome; Cancer
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2009.82

Progress in the management of patients with myelodysplastic syndromes (MDS) has been hampered by the inability to detect cytogenetic abnormalities in 40–60% of cases. We prospectively analyzed matched pairs of bone marrow and buccal cell (normal) DNA samples from 51 MDS patients by single nucleotide polymorphism (SNP) arrays, and identified somatically acquired clonal genomic abnormalities in 21 patients (41%). Among the 33 patients with normal bone marrow cell karyotypes, 5 (15%) had clonal, somatically acquired aberrations by SNP array analysis, including 4 with segmental uniparental disomies (UPD) and 1 with three separate microdeletions. Each abnormality was detected more readily in CD34+ cells than in unselected bone marrow cells. Paired analysis of bone marrow and buccal cell DNA from each patient was necessary to distinguish true clonal genomic abnormalities from inherited copy number variations and regions with apparent loss of heterozygosity. UPDs affecting chromosome 7q were identified in two patients who had a rapidly deteriorating clinical course despite a low-risk International Prognostic Scoring System score. Further studies of larger numbers of patients will be needed to determine whether 7q UPD detected by SNP array analysis will identify higher risk MDS patients at diagnosis, analogous to those with 7q cytogenetic abnormalities.