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

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  • Trine B. Mattesen

    (Aarhus University Hospital)

  • Mads H. Rasmussen

    (Aarhus University Hospital)

  • Juan Sandoval

    (Health Research Institute La Fe (ISSLaFe)
    Health Research Institute La Fe (ISSLaFe))

  • Halit Ongen

    (University of Geneva Medical School-CMU)

  • Sigrid S. Árnadóttir

    (Aarhus University Hospital)

  • Josephine Gladov

    (Aarhus University Hospital)

  • Anna Martinez-Cardus

    (Germans Trias i Pujol Research Institute (IGTP)
    Institute Catalan of Oncology (ICO))

  • Manuel Castro de Moura

    (Josep Carreras Leukaemia Research Institute (IJC))

  • Anders H. Madsen

    (Hospitalsenheden Vest)

  • Søren Laurberg

    (Aarhus University Hospital)

  • Emmanouil T. Dermitzakis

    (University of Geneva Medical School-CMU)

  • Manel Esteller

    (Josep Carreras Leukaemia Research Institute (IJC)
    Centro de Investigacion Biomedica en Red Cancer (CIBERONC)
    Institucio Catalana de Recerca i Estudis Avançats (ICREA)
    University of Barcelona (UB))

  • Claus L. Andersen

    (Aarhus University Hospital)

  • Jesper B. Bramsen

    (Aarhus University Hospital)

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

Suggested Citation

  • Trine B. Mattesen & Mads H. Rasmussen & Juan Sandoval & Halit Ongen & Sigrid S. Árnadóttir & Josephine Gladov & Anna Martinez-Cardus & Manuel Castro de Moura & Anders H. Madsen & Søren Laurberg & Emma, 2020. "MethCORR modelling of methylomes from formalin-fixed paraffin-embedded tissue enables characterization and prognostication of colorectal cancer," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16000-6
    DOI: 10.1038/s41467-020-16000-6
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