Evidence-based genomic diagnosis characterized chromosomal and cryptic imbalances in 30 elderly patients with myelodysplastic syndrome and acute myeloid leukemia
Open Access
- 20 January 2011
- journal article
- Published by Springer Science and Business Media LLC in Molecular Cytogenetics
- Vol. 4 (1), 3
- https://doi.org/10.1186/1755-8166-4-3
Abstract
To evaluate the clinical validity of genome-wide oligonucleotide array comparative genomic hybridization (aCGH) for detecting somatic abnormalities, we have applied this genomic analysis to 30 cases (13 MDS and 17 AML) with clonal chromosomal abnormalities detected in more than 50% of analyzed metaphase cells. The aCGH detected all numerical chromosomal gains and losses from the mainline clones and 113 copy number alterations (CNAs) ranging from 0.257 to 102.519 megabases (Mb). Clinically significant recurrent deletions of 5q (involving the RPS14 gene), 12p12.3 (ETV6 gene), 17p13 (TP53 gene), 17q11.2 (NF1 gene) and 20q, double minutes containing the MYC gene and segmental amplification involving the MLL gene were further characterized with defined breakpoints and gene contents. Genomic features of microdeletions at 17q11.2 were confirmed by FISH using targeted BAC clones. The aCGH also defined break points in a derivative chromosome 6, der(6)t(3;6)(q21.3;p22.2), and an isodicentric X chromosome. However, chromosomally observed sideline clonal abnormalities in five cases were not detected by aCGH. Our data indicated that an integrated cytogenomic analysis will be a better diagnostic scheme to delineate genomic contents of chromosomal and cryptic abnormalities in patients with MDS and AML. An evidence-based approach to interpret somatic genomic findings was proposed.Keywords
This publication has 32 references indexed in Scilit:
- Assessing karyotype precision by microarray-based comparative genomic hybridization in the myelodysplastic/myeloproliferative syndromesMolecular Cytogenetics, 2010
- Genome-Wide Oligonucleotide Array Comparative Genomic Hybridization for Etiological Diagnosis of Mental Retardation: A Multicenter Experience of 1499 Clinical CasesThe Journal of Molecular Diagnostics, 2010
- Detection and Characterization of NF1 Microdeletions by Custom High Resolution Array CGHThe Journal of Molecular Diagnostics, 2009
- Identification of miR-145 and miR-146a as mediators of the 5q– syndrome phenotypeNature Medicine, 2009
- Genomic analysis reveals few genetic alterations in pediatric acute myeloid leukemiaProceedings of the National Academy of Sciences of the United States of America, 2009
- Acquired copy number alterations in adult acute myeloid leukemia genomesProceedings of the National Academy of Sciences of the United States of America, 2009
- Integrated Genomic Analysis Implicates Haploinsufficiency of Multiple Chromosome 5q31.2 Genes in De Novo Myelodysplastic Syndromes PathogenesisPLOS ONE, 2009
- Hidden abnormalities and novel classification of t(15;17) acute promyelocytic leukemia (APL) based on genomic alterationsBlood, 2009
- Frequent genomic abnormalities in acute myeloid leukemia/myelodysplastic syndrome with normal karyotypeHaematologica, 2009
- Identification of RPS14 as a 5q- syndrome gene by RNA interference screenNature, 2008