Comparative analysis of primary tumour and matched metastases in colorectal cancer patients: evaluation of concordance between genomic and transcriptional profiles.
作者： Stéphane Vignot , Céline Lefebvre , Garrett M. Frampton , Guillaume Meurice , Roman Yelensky
DOI: 10.1016/J.EJCA.2015.02.012
关键词:
摘要: Abstract Purpose Focal and temporal tumour heterogeneity can represent a major challenge for biology-guided therapies. This study proposes to investigative molecular discrepancies between primary colorectal cancer (CRC) samples matched metastases. Experimental design Surgical from metastatic tissues 13 CRC patients along with their adjacent normal tissue were evaluated. A mutational analysis was performed using targeted Next Generation Sequencing assay (Foundation Medicine) focus on known recurrent somatic mutations as surrogate of key oncogenic events. Gene expression also investigate transcriptional discrepancies. Results Among the 26 samples, 191 identified including in APC (13 pts), TP53 (11 KRAS (7 pts). Global concordance rate 78% tumours raised 90% 12 CRC. Differential gene revealed low number significantly variant transcripts once effect taken into account. Only two pathways (ST_ADRENERGIC, PID_REELINPATHWAY) differentially up-regulated metastases among 17 pathways. common profile conserved mostly involved cell cycle regulation. down regulated compared control, regulation autophagy (KEGG_REGULATION_OF_AUTOPHAGY). Conclusion These results suggest that profiles identify alterations present at first progression. mainly liver
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