DNA profiling analysis of 100 consecutive de novo acute myeloid leukemia cases reveals patterns of genomic instability that affect all cytogenetic risk groups
| Autor: | Jose A. Marquez, David Blesa, R García, Javier Suela, Sara Alvarez, J C Cigudosa, María Teresa Ardanaz, Francisco Cifuentes, María D. Odero, Maria-Jose Calasanz, Bibiana I. Ferreira, Cristina Largo |
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| Rok vydání: | 2007 |
| Předmět: |
Genome instability
Adult Risk Cancer Research medicine.medical_specialty Gene Dosage Biology Genome Genomic Instability Bone Marrow Acute lymphocytic leukemia medicine Humans Survival analysis Aged Oligonucleotide Array Sequence Analysis Genetics Aged 80 and over Cytogenetics Myeloid leukemia Karyotype Hematology Middle Aged medicine.disease Prognosis Oncology DNA profiling Leukemia Myeloid Acute Disease Cytogenetic Analysis Mutation |
| Zdroj: | Leukemia. 21(6) |
| ISSN: | 0887-6924 |
| Popis: | We have carried out a high-resolution whole genome DNA profiling analysis on 100 bone marrow samples from a consecutive series of de novo acute myeloid leukemia (AML) cases. After discarding copy number changes that are known to be genetic polymorphisms, we found that genomic aberrations (GA) in the form of gains or losses of genetic material were present in 74% of the samples, with a median of 2 GA per case (range 0–35). In addition to the cytogenetically detected aberration, GA were present in cases from all cytogenetic prognostic groups: 79% in the favorable group, 60% in the intermediate group (including 59% of cases with normal karyotype) and 83% in the adverse group. Five aberrant deleted regions were recurrently associated with cases with a highly aberrant genome (e.g., a 1.5 Mb deletion at 17q11.2 and a 750 kb deletion at 5q31.1). Different degrees of genomic instability showed a statistically significant impact on survival curves, even within the normal karyotype cases. This association was independent of other clinical and genetic parameters. Our study provides, for the first time, a detailed picture of the nature and frequency of DNA copy number aberrations in de novo AML. |
| Databáze: | OpenAIRE |
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