Altered gene expression in multiple myeloma patients with gain of 1q21 locus.
|Fakulta / Pracoviště MU|
|Popis||Chromosome 1 abnormalities namely gain of 1q21 locus is one of the few cytogenetic factors with unfavourable prognostic impact in patients with MM. We analysed gene expression in patients with/without 1q21 gain. The 1q21 gain status was evaluated in 34 patients by FISH and confirmed by arrayCGH (Agilent Human Genome CGH Microarray, 4x44k) when DNA was available. CD138+ cells were separated by MACS. Total RNA was transcribed into cDNA (Ambion WT Sense Target assay), labeled and hybridized to the Affymetrix GeneChip Human Gene ST 1.0 array. Acquisition of Affymetrix array images, RMA normalization algorithm, t-test with Benjamini-Hochberg FDR were performed using appropriate software. The 1q21 gain was detected in 50% (17/34) cases. When comparing expression of patients with/without 1q21 gain, total of 63 transcripts showed altered expression. We found 27 differentialy expressed transcripts with FC<1.5 (22 up, and 5 down), 17 of over-expressed transcripts were mapped exactly to chromosome 1. The most altered expression (FC>2.0, p<0.05) showed increase of UCHL1 (ubiquitin thiolesterase), GPR63 (G-protein receptor), TUBB4 (tubulin), KIF21B (kinesin) and decrease of STAP1, MAML2, FAM13A and PDE4B (phosphodiesterase), respectively. Based on ontology of revealed genes with altered expression, we anticipate that patients with 1q21 gain might have increased microtubules activity and/or dysregulation of G-protein associated signal transduction. This may reflect the pathogenesis of multiple myeloma.|