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BMC Medical Genomics

, 2:53

First Online: 17 August 2009Received: 30 September 2008Accepted: 17 August 2009

Abstract

BackgroundOne of the most striking features of the childhood malignancy neuroblastoma NB is its clinical heterogeneity. Although there is a great need for better clinical and biological markers to distinguish between tumours with different severity and to improve treatment, no clear-cut prognostic factors have been found. Also, no major NB tumour suppressor genes have been identified.

MethodsIn this study we performed expression analysis by quantitative real-time PCR QPCR on primary NB tumours divided into two groups, of favourable and unfavourable outcome respectively. Candidate genes were selected on basis of lower expression in unfavourable tumour types compared to favourables in our microarray expression analysis. Selected genes were studied in two steps: 1 using TaqMan Low Density Arrays TLDA targeting 89 genes on a set of 12 NB tumour samples, and 2 12 genes were selected from the TLDA analysis for verification using individual TaqMan assays in a new set of 13 NB tumour samples.

ResultsBy TLDA analysis, 81 out of 87 genes were found to be significantly differentially expressed between groups, of which 14 have previously been reported as having an altered gene expression in NB. In the second verification round, seven out of 12 transcripts showed significantly lower expression in unfavourable NB tumours, ATBF1, CACNA2D3, CNTNAP2, FUSIP1, GNB1, SLC35E2, and TFAP2B. The gene that showed the highest fold change in the TLDA analysis, POU4F2, was investigated for epigenetic changes CpG methylation and mutations in order to explore the cause of the differential expression. Moreover, the fragile site gene CNTNAP2 that showed the largest fold change in verification group 2 was investigated for structural aberrations by copy number analysis. However, the analyses of POU4F2 and CNTNAP2 showed no genetic alterations that could explain a lower expression in unfavourable NB tumours.

ConclusionThrough two steps of verification, seven transcripts were found to significantly discriminate between favourable and unfavourable NB tumours. Four of the transcripts, CACNA2D3, GNB1, SLC35E2, and TFAP2B, have been observed in previous microarray studies, and are in this study independently verified. Our results suggest these transcripts to be markers of malignancy, which could have a potential usefulness in the clinic.

Electronic supplementary materialThe online version of this article doi:10.1186-1755-8794-2-53 contains supplementary material, which is available to authorized users.

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Autor: Kaisa Thorell - Annika Bergman - Helena Carén - Staffan Nilsson - Per Kogner - Tommy Martinsson - Frida Abel

Fuente: https://link.springer.com/



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