Identification of prognostic relevant chromosomal abnormalities in chronic lymphocytic leukemia using microarray-based genomic profiling

Autor: Trijnie Dijkhuizen, Marian Stevens-Kroef, Eva van den Berg, Ad Geurts van Kessel, Marloes Benjamins, Patricia J. T. A. Groenen, Annet Simons, Daniel Olde Weghuis, Matty Linssen-Wiersma, Rolph Pfundt
Jazyk: angličtina
Rok vydání: 2014
Předmět:
medicine.medical_specialty
SNP ARRAY
Microarray
Biology
Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9]
HEMATOLOGICAL MALIGNANCIES
ABERRATIONS
Biochemistry
Loss of heterozygosity
Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2]
FISH
Genetics
medicine
Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14]
TOOL
Genetics(clinical)
Multiplex
Multiplex ligation-dependent probe amplification
Molecular Biology
Genetics (clinical)
Biochemistry
medical
medicine.diagnostic_test
Research
DELETION
Biochemistry (medical)
Cytogenetics
REARRANGEMENT
CYTOGENETICS
Human genetics
MLPA
Molecular Medicine
Chronic lymphocytic leukemia
Microarray-based genomic profiling
Neurodevelopmental disorders Radboud Institute for Molecular Life Sciences [Radboudumc 7]
HYBRIDIZATION
CLL
SNP array
Fluorescence in situ hybridization
Zdroj: Molecular Cytogenetics, 7, 1, pp. 3
Molecular Cytogenetics, 7:3. BMC
Molecular Cytogenetics, 7, 3
Molecular Cytogenetics
ISSN: 1755-8166
Popis: Contains fulltext : 138213.pdf (Publisher’s version ) (Open Access) BACKGROUND: Characteristic genomic abnormalities in patients with B cell chronic lymphocytic leukemia (CLL) have been shown to provide important prognostic information. Fluorescence in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA), currently used in clinical diagnostics of CLL, are targeted tests aimed at specific genomic loci. Microarray-based genomic profiling is a new high-resolution tool that enables genome-wide analyses. The aim of this study was to compare two recently launched genomic microarray platforms, i.e., the CytoScan HD Array (Affymetrix) and the HumanOmniExpress Array (Illumina), with FISH and MLPA to ascertain whether these latter tests can be replaced by either one of the microarray platforms in a clinical diagnostic setting. RESULT: Microarray-based genomic profiling and FISH were performed in all 28 CLL patients. For an unbiased comparison of the performance of both microarray platforms 9 patients were evaluated on both platforms, resulting in the identification of exactly identical genomic aberrations. To evaluate the detection limit of the microarray platforms we included 7 patients in which the genomic abnormalities were present in a relatively low percentage of the cells (range 5-28%) as previously determined by FISH. We found that both microarray platforms allowed the detection of copy number abnormalities present in as few as 16% of the cells. In addition, we found that microarray-based genomic profiling allowed the identification of genomic abnormalities that could not be detected by FISH and/or MLPA, including a focal TP53 loss and copy neutral losses of heterozygosity of chromosome 17p. CONCLUSION: From our results we conclude that although the microarray platforms exhibit a somewhat lower limit of detection compared to FISH, they still allow the detection of copy number abnormalities present in as few as 16% of the cells. By applying similar interpretation criteria, the results obtained from both platforms were comparable. In addition, we conclude that both microarray platforms allow the identification of additional potential prognostic relevant abnormalities such as focal TP53 deletions and copy neutral losses of heterozygosity of chromosome 17p, which would have remained undetected by FISH or MLPA. The prognostic relevance of these novel genomic alterations requires further evaluation in prospective clinical trials.
Databáze: OpenAIRE
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