Effect of DNA Dosage into Gene Expression in Patients with Multiple Myeloma
| Autoři | |
|---|---|
| Rok publikování | 2013 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Whole genomic methods represents effective tool for studying genomic changes in cancer cells. Aim of this study was to find and describe genes whose expression is dependent on the DNA copy number (gene dosage) in patients with multiple myeloma. Total of 57 patients with MM were simultaneously examined by arrayCGH for DNA copy number variations (gain/losses) utilizing Agilent Human Genome CGH Microarray 4x44K Arrays and for gene expression utilizing Affymetrix GeneChip Human Gene 1.0 ST. Gene dosage-dependent genes were defined by Spearman correlation[R>0.5, p(FDR)<0.05]of CNV status and expression level and analysed using DAVID Bioinformatics software. Total of 852 fromall 27391 transcripts were strongly and significantly dependent ongene dosage. Cytogeneticaly, majority (25%) of all 852 genes were located on chromosome 1 (with 19 genes mapped to 1q21 locus). Other involved genes were mostly located on chromosomes 15 (8.7%), 19 (8.7%), and chromosome 13 (8.6%). Pathway analysis showed most genes to be involved in PDGF pathway, ubiquitin proteasome pathway, Ras pathway and TNFR1 signaling pathway. Although almost all chromosomes have been at least once affected by either gain or loss of genetic material, number of genes with affected exrrpession is relatively low. We anticipate two mechanism for expression level compensations: i) increase of related supressors activity in case of gains ii) impact of second allele in case of losses. |
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