Molecular cytogenetic profiling of complex karyotypes in primary myelodysplastic syndromes and acute myeloid leukemia

Trost, Detlef; Hildebrandt, Barbara; Beier, Manfred; Müller, Nicola; Germing, Ulrich; Royer‐Pokora, Brigitte

doi:10.1016/j.cancergencyto.2005.09.007

Cited by 29 publications

(14 citation statements)

References 24 publications

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“…[24][25][26][27][28][29] These studies demonstrate that FISH analysis can provide additional information about chromosome 5 abnormalities. It would, therefore, be recommendable to use FISH techniques to study those cases with monosomy 5 and/or marker chromosomes in order to identify translocations with a breakpoint in 5q or possible 5q-chromosomes.…”

Section: Discussionmentioning

confidence: 99%

Fluorescence in situ hybridization improves the detection of 5q31 deletion in myelodysplastic syndromes without cytogenetic evidence of 5q-

Mallo¹,

Arenillas²,

Espinet³

et al. 2008

Haematologica

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BackgroundMore than 50% of patients with myelodysplastic syndromes present cytogenetic aberrations at diagnosis. Partial or complete deletion of the long arm of chromosome 5 is the most frequent abnormality. The aim of this study was to apply fluorescence in situ hybridization of 5q31 in patients diagnosed with de novo myelodysplastic syndromes in whom conventional banding cytogenetics study had shown a normal karyotype, absence of metaphases or an abnormal karyotype without evidence of del(5q). Design and MethodsWe performed fluorescence in situ hybridization of 5q31 in 716 patients, divided into two groups: group A patients (n=637) in whom the 5q deletion had not been detected at diagnosis by conventional banding cytogenetics and group B patients (n=79), in whom cytogenetic analysis had revealed the 5q deletion (positive control group). ResultsIn group A (n=637), the 5q deletion was detected by fluorescence in situ hybridization in 38 cases (5.96%). The majority of positive cases were diagnosed as having the 5q-syndrome. The deletion was mainly observed in cases in which the cytogenetics study had shown no metaphases or an aberrant karyotype with chromosome 5 involved. In group B (n=79), the 5q deletion had been observed by cytogenetics and was confirmed to be present in all cases by fluorescence in situ hybridization of 5q31. ConclusionsFluorescence in situ hybridization of 5q31 detected the 5q deletion in 6% of cases without clear evidence of del(5q) by conventional banding cytogenetics. We suggest that fluorescence in situ hybridization of 5q31 should be performed in cases of a suspected '5q-syndrome' and/or if the cytogenetic study shows no metaphases or an aberrant karyotype with chromosome 5 involved (no 5q-chromosome).

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Section: Discussionmentioning

confidence: 99%

Fluorescence in situ hybridization improves the detection of 5q31 deletion in myelodysplastic syndromes without cytogenetic evidence of 5q-

Mallo¹,

Arenillas²,

Espinet³

et al. 2008

Haematologica

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“…31,32 Other molecular cytogenetic techniques have also unveiled new chromosomal rearrangements which were not visible by karyotyping. [16][17][18][19]33,34 We have used a genomic array with more than 40 000 probes that offers a median resolution of 75 kb and whose composition is biased towards known genes. 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.…”

Section: Discussionmentioning

confidence: 99%

“…5q has been widely studied in myeloid leukemias, being an important marker of karyotype complexity. 34,42 Genes included in the deleted 5q31.1 region are PPP2CA, SKP1A, UBE2B and CDKL3. PPP2CA, the isoform a of the catalytic subunit of the protein phosphatase 2, has been shown to play a crucial role in DNA repair: loss of function of this phosphatase leads to inefficient DNA repair and to further hypersensibility to DNA damage.…”

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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“…Metaphase chromosomes were prepared following standard procedures. Giemsa karyotypes were generated according to International System for Human Cytogenic Nomenclature (12), and fluorescence in situ hybridizations (FISH) were performed as described (13). PAC/BAC probes were from (Genome Systems; imaGenes).…”

Section: Methodsmentioning

confidence: 99%

Hyperactivation of the Insulin-like Growth Factor Receptor I Signaling Pathway Is an Essential Event for Cisplatin Resistance of Ovarian Cancer Cells

Eckstein

Servan

Hildebrandt³

et al. 2009

Cancer Research

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143

127

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Platinum plays a central role in the therapy of ovarian cancer, and the emergence of platinum resistance is a major obstacle for clinical management of the disease. We treated A2780 ovarian cancer cells by weekly cycles of cisplatin over a period of 6 months and unveiled that enhanced insulin-like growth factor I receptor (IGF-IR) expression and autocrine IGF-I are associated with hyperactivation of the IGF-IR and phosphatidylinositol-3-OH kinase (PI3K) pathways in cisplatinresistant cells. IGF-IR expression levels increased during treatment cycles and correlated with cisplatin resistance. Purified IGF-I induced cisplatin resistance in diverse ovarian cancer cell lines, and small molecule inhibitors proved that IGF-IR and PI3K are essential for cisplatin resistance. Similar results were obtained with BG-1 ovarian cancer cells. Cytogenetic and array comparative genomic hybridization analyses revealed selection and de novo formation of chromosomal alterations during resistance development. An analysis of gene expression profiles of primary ovarian carcinomas identified the regulatory subunit PIK3R2 of PI3-kinase as a significant negative prognosis factor for ovarian cancer. We conclude that targeting the IGF-IR and the PI3K pathways is a promising new strategy to treat cisplatinresistant ovarian carcinomas.

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Molecular cytogenetic profiling of complex karyotypes in primary myelodysplastic syndromes and acute myeloid leukemia

Cited by 29 publications

References 24 publications

Fluorescence in situ hybridization improves the detection of 5q31 deletion in myelodysplastic syndromes without cytogenetic evidence of 5q-

Fluorescence in situ hybridization improves the detection of 5q31 deletion in myelodysplastic syndromes without cytogenetic evidence of 5q-

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

Hyperactivation of the Insulin-like Growth Factor Receptor I Signaling Pathway Is an Essential Event for Cisplatin Resistance of Ovarian Cancer Cells

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