TAILIEUCHUNG - báo cáo khoa học: " Transcriptome instability in colorectal cancer identified by exon microarray analyses: Associations with splicing factor expression levels and patient survival"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Transcriptome instability in colorectal cancer identified by exon microarray analyses: Associations with splicing factor expression levels and patient survival | Sveen et al. Genome Medicine 2011 3 32 http content 3 5 32 Genome Medicine RESEARCH Open Access Transcriptome instability in colorectal cancer identified by exon microarray analyses Associations with splicing factor expression levels and patient survival Anita Sveen1 21 Trude H Ảgesen1 21 Arild Nesbakken2 3 Torleiv O Rognum4 Ragnhild A Lothe1 2 and Rolf I Skotheim1 2 Abstract Background Colorectal cancer CRC is a heterogeneous disease that on the molecular level can be characterized by inherent genomic instabilities chromosome instability and microsatellite instability. In the present study we analyze genome-wide disruption of pre-mRNA splicing and propose transcriptome instability as a characteristic that is analogous to genomic instability on the transcriptome level. Methods Exon microarray profiles from two independent series including a total of 160 CRCs were investigated for their relative amounts of exon usage differences. Each exon in each sample was assigned an alternative splicing score calculated by the FIRMA algorithm. Amounts of deviating exon usage per sample were derived from exons with extreme splicing scores. Results There was great heterogeneity within both series in terms of sample-wise amounts of deviating exon usage. This was strongly associated with the expression levels of approximately half of 280 splicing factors 54 and 48 of splicing factors were significantly correlated to deviating exon usage amounts in the two series . Samples with high or low amounts of deviating exon usage associated with overall transcriptome instability were almost completely separated into their respective groups by hierarchical clustering analysis of splicing factor expression levels in both sample series. Samples showing a preferential tendency towards deviating exon skipping or inclusion were associated with skewed transcriptome instability. There were significant associations between transcriptome instability and reduced patient survival in .

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