MethCORR modelling of methylomes from formalin-fixed paraffin-embedded tissue enables characterization and prognostication of colorectal cancer
Mattesen, Trine B. ![Identificador ORCID](/img/uab/orcid.ico)
(Aarhus University Hospital (Aarhus, Dinamarca))
Rasmussen, M. H. ![Identificador ORCID](/img/uab/orcid.ico)
(Aarhus University Hospital (Aarhus, Dinamarca))
Sandoval, Juan ![Identificador ORCID](/img/uab/orcid.ico)
(Instituto de Investigación Sanitaria La Fe)
Ongen, H. ![Identificador ORCID](/img/uab/orcid.ico)
(Genetic Medicine and Development. University of Geneva Medical School-CMU)
Árnadóttir, Sigrid S. (Aarhus University Hospital (Aarhus, Dinamarca))
Gladov, Josephine ![Identificador ORCID](/img/uab/orcid.ico)
(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
Data: |
2020 |
Resum: |
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. |
Ajuts: |
European Commission 258236
|
Drets: |
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. ![Creative Commons](/img/licenses/by.ico) |
Llengua: |
Anglès |
Document: |
Article ; recerca ; Versió publicada |
Matèria: |
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 |
Publicat a: |
Nature communications, Vol. 11 Núm. 1 (january 2020) , p. 2025, ISSN 2041-1723 |
DOI: 10.1038/s41467-020-16000-6
PMID: 32332866
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Registre creat el 2021-02-12, darrera modificació el 2024-06-13