MethCORR modelling of methylomes from formalin-fixed paraffin-embedded tissue enables characterization and prognostication of colorectal cancer.

Autor:	Mattesen TB; Department of Molecular Medicine, Aarhus University Hospital, 8200, Aarhus, Denmark., Rasmussen MH; Department of Molecular Medicine, Aarhus University Hospital, 8200, Aarhus, Denmark., Sandoval J; Epigenomic Unit, Health Research Institute La Fe (ISSLaFe), Valencia, Spain.; Biomarker and precision medicine Unit, Health Research Institute La Fe (ISSLaFe), Valencia, Spain., Ongen H; Genetic Medicine and Development, University of Geneva Medical School-CMU, 1 Rue Michel-Servet, 1211, Geneva, Switzerland., Árnadóttir SS; Department of Molecular Medicine, Aarhus University Hospital, 8200, Aarhus, Denmark., Gladov J; Department of Molecular Medicine, Aarhus University Hospital, 8200, Aarhus, Denmark., Martinez-Cardus A; Badalona Applied Research Group in Oncology (B-ARGO), Germans Trias i Pujol Research Institute (IGTP), Badalona, Barcelona, Catalonia, Spain.; Medical Oncology Service, Institute Catalan of Oncology (ICO), Badalona, Barcelona, Catalonia, Spain., Castro de Moura M; Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain., Madsen AH; Department of Surgery, Hospitalsenheden Vest, 7400, Herning, Denmark., Laurberg S; Colorectal Surgical Unit, Department of Surgery, Aarhus University Hospital, 8200, Aarhus, Denmark., Dermitzakis ET; Genetic Medicine and Development, University of Geneva Medical School-CMU, 1 Rue Michel-Servet, 1211, Geneva, Switzerland., Esteller M; Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain.; Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain.; Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.; Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Catalonia, Spain., Andersen CL; Department of Molecular Medicine, Aarhus University Hospital, 8200, Aarhus, Denmark. Cla@clin.au.dk., Bramsen JB; Department of Molecular Medicine, Aarhus University Hospital, 8200, Aarhus, Denmark. Bramsen@clin.au.dk.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2020 Apr 24; Vol. 11 (1), pp. 2025. Date of Electronic Publication: 2020 Apr 24.
DOI:	10.1038/s41467-020-16000-6
Abstrakt:	Transcriptional characterization and classification has potential to resolve the inter-tumor heterogeneity of colorectal cancer and improve patient management. Yet, robust transcriptional profiling is difficult using formalin-fixed, paraffin-embedded (FFPE) samples, which complicates testing in clinical and archival material. We present MethCORR, an approach that allows uniform molecular characterization and classification of fresh-frozen and FFPE samples. MethCORR identifies genome-wide correlations between RNA expression and DNA methylation in fresh-frozen samples. This information is used to infer gene expression information in FFPE samples from their methylation profiles. MethCORR is here applied to methylation profiles from 877 fresh-frozen/FFPE samples and comparative analysis identifies the same two subtypes in four independent cohorts. Furthermore, subtype-specific prognostic biomarkers that better predicts relapse-free survival (HR = 2.66, 95%CI [1.67-4.22], P value < 0.001 (log-rank test)) than UICC tumor, node, metastasis (TNM) staging and microsatellite instability status are identified and validated using DNA methylation-specific PCR. The MethCORR approach is general, and may be similarly successful for other cancer types.
Databáze:	MEDLINE
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