The use of long-oligonucleotide microarray-based comparative genomic hybridization in prediction of clinical outcome of B-cell chronic lymphocytic leukemia
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| Year of publication | 2007 |
| Type | Conference abstract |
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| Description | One of the many ways, in which gene expression and function may be modified is alteration in DNA copy number. Some variations are found among normal individuals, others participate in causing various disease states. DNA dosage-alteration changes occurring in somatic cells are frequent contributors to cancer. In cancer, genes detrimental to tumor growth (e.g. tumor suppressor genes) are likely to be contained in regions of decreased DNA copy number; while genes important for tumor growth or development (e.g. oncogenes) are likely to be contained in regions of increased DNA copy number. In B-cell chronic lymphocytic leukemia (B-CLL) most cytogenetic studies detected deletions involving chromosome band 13q14 (where miRNAs 15 and 16 are located) to be the most frequent chromosome aberration. Other frequent aberrations are deletions of 11q22.3-q23.1 (genomic region where gene ATM is located), trisomy 12, deletions of 6q21-q23, and deletions/mutations of the TP53 tumor suppressor gene at 17p13. The evaluation of the incidence of these aberrations provides the basis for more accurate correlations with clinical characteristics and outcome. DNA copy number changes can be detected by comparative genomic hybridization (CGH), a fluorescent molecular cytogenetic technique mapping these variations to normal metaphase chromosomes. The introduction of microarray based comparative genomic hybridization (arrayCGH) provided a powerful tool to precisely detect and quantify genomic aberrations and map these directly onto the sequence of the human genome. Long oligo-based microarrays hold the potential of enhanced design flexibility and eventual full-genome representation of probes capable of accurately reporting single-copy number changes compared to bacterial artificial chromosome (BAC)-based and cDNA-based arrays. Oligonucleotide-array probes can be designed in silico for any sequenced region of a genome. On our clinical samples we demonstrate that long-oligonucleotide array CGH not only confirmed the results obtained from cytogenetic CGH, but also discovered more copy number alterations, not found with cytogenetic CGH on the set of samples investigated on B-CLL. The application of these molecular cytogenetic techniques will also contribute to the identification of the pathogenetically relevant genes that are affected by the chromosome aberrations in B-CLL. |