The pan-cancer pathological regulatory landscape
Por:
M. FALCO, M. BLEDA, J. CARBONELL-CABALLERO and J. DOPAZO
Publicada:
21 dic 2016
Resumen:
Dysregulation of the normal gene expression program is the cause of a broad range of diseases, including cancer. Detecting the specific perturbed regulators that have an effect on the generation and the development of the disease is crucial for understanding the disease mechanism and for taking decisions on efficient preventive and curative therapies. Moreover, detecting such perturbations at the patient level is even more important from the perspective of personalized medicine. We applied the Transcription Factor Target Enrichment Analysis, a method that detects the activity of transcription factors based on the quantification of the collective transcriptional activation of their targets, to a large collection of 5607 cancer samples covering eleven cancer types. We produced for the first time a comprehensive catalogue of altered transcription factor activities in cancer, a considerable number of them significantly associated to patient's survival. Moreover, we described several interesting TFs whose activity do not change substantially in the cancer with respect to the normal tissue but ultimately play an important role in patient prognostic determination, which suggest they might be promising therapeutic targets. An additional advantage of this method is that it allows obtaining personalized TF activity estimations for individual patients.
Filiaciones:
M. FALCO:
CIPF, Computat Genom Dept, Valencia 46012, Spain
M. BLEDA:
Univ Cambridge, Dept Med, Sch Clin Med, Addenbrookes Hosp, Hills Rd, Cambridge CB2 0QQ, England
:
CIPF, Computat Genom Dept, Valencia 46012, Spain
:
CIPF, Computat Genom Dept, Valencia 46012, Spain
Funct Genom Node INB ELIXIR Es, C Eduardo Primo Yufera 3, Valencia 46012, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Bioinformat Rare Dis BiER, C Eduardo Primo Yufera 3, Valencia 46012, Spain
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