MethCORR modelling of methylomes from formalin-fixed paraffin-embedded tissue enables characterization and prognostication of colorectal cancer
Mattesen, Trine B. (Aarhus University Hospital (Aarhus, Dinamarca))
Rasmussen, M. H. (Aarhus University Hospital (Aarhus, Dinamarca))
Sandoval, Juan (Instituto de Investigación Sanitaria La Fe)
Ongen, H. (Genetic Medicine and Development. University of Geneva Medical School-CMU)
Árnadóttir, Sigrid S. (Aarhus University Hospital (Aarhus, Dinamarca))
Gladov, Josephine (Aarhus University Hospital (Aarhus, Dinamarca))
Martínez Cardús, Anna (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Castro de Moura, Manuel (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Madsen, Anders H. (Department of Surgery. Hospitalsenheden Vest)
Laurberg, Søren (Aarhus University Hospital (Aarhus, Dinamarca))
Dermitzakis, Emmanouil T (University of Geneva Medical School)
Esteller, M. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Andersen, Claus Lindbjerg (Aarhus University Hospital (Aarhus, Dinamarca))
Bramsen, Jesper Bertram (Aarhus University Hospital (Aarhus, Dinamarca))
Universitat Autònoma de Barcelona

Date:	2020
Abstract:	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.
Grants:	European Commission 258236
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Aged ; Biomarkers, Tumor ; Colon ; Colorectal Neoplasms ; Datasets as Topic ; Disease-Free Survival ; DNA Methylation ; Epigenome ; Female ; Formaldehyde ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Intestinal Mucosa ; Male ; Middle Aged ; Models, Genetic ; Neoplasm Recurrence, Local ; Paraffin Embedding ; Prognosis ; Rectum ; Risk Assessment ; Tissue Fixation
Published in:	Nature communications, Vol. 11 Núm. 1 (january 2020) , p. 2025, ISSN 2041-1723

DOI: 10.1038/s41467-020-16000-6
PMID: 32332866

15 p, 2.9 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Articles > Research articles
Articles > Published articles