Putative cis-regulatory drivers in colorectal cancer

• Tipo: Artigo em Revista Científica Internacional
• Data: 2014

Autores

Ongen, H (Autor) Outra; Andersen, CL (Autor) Outra; Bramsen, JB (Autor) Outra; Oster, B (Autor) Outra; Rasmussen, MH (Autor) Outra; Ferreira, PG (Autor) Outra; Sandoval, J (Autor) Outra; Vidal, E (Autor) Outra; Whiffin, N (Autor) Outra; Planchon, A (Autor) Outra; Padioleau, I (Autor) Outra; Bielser, D (Autor) Outra; Romano, L (Autor) Outra; Tomlinson, I (Autor) Outra; Houlston, RS (Autor) Outra; Esteller, M (Autor) Outra; Orntoft, TF (Autor) Outra; Dermitzakis, ET (Autor) Outra

Revista

Título: Nature

Vol. 512

Páginas: 87-90

ISSN: 0028-0836

Editora: Springer Nature

Indexação

Scopus - 105 Citações

Classificação Científica

CORDIS: Ciências Naturais > Ciências biológicas > Biologia > Biologia computacional ; Ciências Naturais > Ciências biológicas > Biologia > Biologia molecular

FOS: Ciências exactas e naturais > Ciências biológicas ; Ciências exactas e naturais > Ciências da computação e da informação

Outras Informações

ID Authenticus: P-00Q-55J

DOI: 10.1038/nature13602

Abstract (EN): The cis-regulatory effects responsible for cancer development have not been as extensively studied as the perturbations of the protein coding genome in tumorigenesis. To better characterize colorectal cancer (CRC) development we conducted an RNA-sequencing experiment of 103 matched tumour and normal colon mucosa samples from Danish CRC patients, 90 of which were germline-genotyped. By investigating allele-specific expression (ASE) we show that the germline genotypes remain important determinants of allelic gene expression in tumours. Using the changes in ASE in matched pairs of samples we discover 71 genes with excess of somatic cis-regulatory effects in CRC, suggesting a cancer driver role. We correlate genotypes and gene expression to identify expression quantitative trait loci (eQTLs) and find 1,693 and 948 eQTLs in normal samples and tumours, respectively. We estimate that 36% of the tumour eQTLs are exclusive to CRC and show that this specificity is partially driven by increased expression of specific transcription factors and changes in methylation patterns. We show that tumour-specific eQTLs are more enriched for low CRC genome-wide association study (GWAS) P values than shared eQTLs, which suggests that some of the GWAS variants are tumour specific regulatory variants. Importantly, tumour-specific eQTL genes also accumulate more somatic mutations when compared to the shared eQTL genes, raising the possibility that they constitute germline-derived cancer regulatory drivers. Collectively the integration of genome and the transcriptome reveals a substantial number of putative somatic and germline cis-regulatory cancer changes that may have a role in tumorigenesis.

Idioma: Inglês

Tipo (Avaliação Docente): Científica