Oligonucleotide array-CGH reveals cryptic gene copy number alterations in karyotypically normal acute myeloid leukemia

Tyybäkinoja, Anne; Elonen, Erkki; Piippo, Kirsi; Porkka, Kimmo; Knuutila, Sakari

doi:10.1038/sj.leu.2404543

Cited by 46 publications

(37 citation statements)

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“…We have analyzed 100 samples from a series of consecutively ascertained cases, an optimal experimental design that provides a comprehensive and complete picture of the genomic features of the disease. Previous studies dealing with the genomic characterization of AML have been reported, but have failed either to cover all the cytogenetic subtypes 18,19,35 or to provide a complete high resolution description of gained and deleted regions that occurred in their series because they were based on SNP-array technology and focused exclusively on the loss of heterozygosity analysis. 15 Array CGH in de novo AML J Suela et al…”

Section: Discussionmentioning

confidence: 99%

DNA profiling analysis of 100 consecutive de novo acute myeloid leukemia cases reveals patterns of genomic instability that affect all cytogenetic risk groups

et al. 2007

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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.

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Section: Discussionmentioning

confidence: 99%

DNA profiling analysis of 100 consecutive de novo acute myeloid leukemia cases reveals patterns of genomic instability that affect all cytogenetic risk groups

et al. 2007

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“…The copy number ratios (log2 ratios) obtained from GTYPE 4.1 were imported to CGH Analytics software v3.4.27 (Agilent Technologies, Palo Alto, California) to obtain uniform data with previously reported 44K CGH oligonucleotide microarray (Agilent Technologies) results of the same sample set. 4 The SNP experiments were confirmed using the apparent LOH of the X chromosomes in male patients versus the female controls. The FLT3 mutation analyses had been performed previously.…”

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confidence: 83%

“…2 However, array-CGH (aCGH), a high-resolution method for genome-wide DNA copy number change detection, has revealed cryptic alterations in 15-59% of karyotypically normal AML. 3,4 Loss of heterozygozity (LOH), identified as allelic imbalance in polymorphic loci, is frequently observed in cancers and is thought to result from genomic losses or gains leading to unequal ratios of parental alleles. However, copy number neutral alteration may result in apparent LOH, i.e., acquired uniparental disomy (UPD), where one of the parental alleles is lost while the other is duplicated.…”

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confidence: 99%

“…The FLT3 mutation analyses had been performed previously. 4 LOH was detected in 12/19 (63%) of the cases (Online Supplementary Appendix, Table 1). Recurrent LOH was detected in 7q (2 cases) and 13q (3 cases).…”

mentioning

confidence: 99%

“…In the present study, the SNP arrays revealed LOH and copy number amplification at 8q24.13-q24.22 in one sample (#14), which previous FISH and aCGH studies had proven to harbor an extrachromosomal amplification of 4.1 Mb including MYC. 4 LOH of the region indicated that one allele was preferably amplified. The mechanisms of UPD in AML pathogenesis might be associated with genetic or epigenetic alterations of tumor suppressor genes that reside in the region of LOH.…”

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confidence: 99%

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