Academic Journal
The landscape of selection in 551 esophageal adenocarcinomas defines genomic biomarkers for the clinic
| Τίτλος: | The landscape of selection in 551 esophageal adenocarcinomas defines genomic biomarkers for the clinic |
|---|---|
| Συγγραφείς: | Frankell, AM, Jammula, S, Li, X, Contino, G, Killcoyne, S, Abbas, S, Perner, J, Bower, L, Devonshire, G, Ococks, E, Grehan, N, Mok, J, O'Donovan, M, MacRae, S, Eldridge, MD, Tavaré, S, Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS, ., Fitzgerald, RC |
| Πηγή: | Nature Genetics , 51 pp. 506-516. (2019) |
| Έτος έκδοσης: | 2019 |
| Συλλογή: | University College London: UCL Discovery |
| Θεματικοί όροι: | Bioinformatics, Gastrointestinal cancer, Genomics, Oesophageal diseases, Translational research |
| Περιγραφή: | Esophageal adenocarcinoma (EAC) is a poor-prognosis cancer type with rapidly rising incidence. Understanding of the genetic events driving EAC development is limited, and there are few molecular biomarkers for prognostication or therapeutics. Using a cohort of 551 genomically characterized EACs with matched RNA sequencing data, we discovered 77 EAC driver genes and 21 noncoding driver elements. We identified a mean of 4.4 driver events per tumor, which were derived more commonly from mutations than copy number alterations, and compared the prevelence of these mutations to the exome-wide mutational excess calculated using non-synonymous to synonymous mutation ratios (dN/dS). We observed mutual exclusivity or co-occurrence of events within and between several dysregulated EAC pathways, a result suggestive of strong functional relationships. Indicators of poor prognosis (SMAD4 and GATA4) were verified in independent cohorts with significant predictive value. Over 50% of EACs contained sensitizing events for CDK4 and CDK6 inhibitors, which were highly correlated with clinically relevant sensitivity in a panel of EAC cell lines and organoids. |
| Τύπος εγγράφου: | article in journal/newspaper |
| Περιγραφή αρχείου: | text |
| Γλώσσα: | English |
| Relation: | https://discovery.ucl.ac.uk/id/eprint/10069342/10/Lovat_The%20landscape%20of%20selection%20in%20551%20esophageal%20adenocarcinomas%20defines%20genomic%20biomarkers%20for%20the%20clinic_AAM2.pdf; https://discovery.ucl.ac.uk/id/eprint/10069342/ |
| Διαθεσιμότητα: | https://discovery.ucl.ac.uk/id/eprint/10069342/10/Lovat_The%20landscape%20of%20selection%20in%20551%20esophageal%20adenocarcinomas%20defines%20genomic%20biomarkers%20for%20the%20clinic_AAM2.pdf https://discovery.ucl.ac.uk/id/eprint/10069342/ |
| Rights: | open |
| Αριθμός Καταχώρησης: | edsbas.24B117F0 |
| Βάση Δεδομένων: | BASE |
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