Pan-cancer image-based detection of clinically actionable genetic alterations.

Journal: Nature cancer
Published Date:

Abstract

Molecular alterations in cancer can cause phenotypic changes in tumor cells and their micro-environment. Routine histopathology tissue slides - which are ubiquitously available - can reflect such morphological changes. Here, we show that deep learning can consistently infer a wide range of genetic mutations, molecular tumor subtypes, gene expression signatures and standard pathology biomarkers directly from routine histology. We developed, optimized, validated and publicly released a one-stop-shop workflow and applied it to tissue slides of more than 5000 patients across multiple solid tumors. Our findings show that a single deep learning algorithm can be trained to predict a wide range of molecular alterations from routine, paraffin-embedded histology slides stained with hematoxylin and eosin. These predictions generalize to other populations and are spatially resolved. Our method can be implemented on mobile hardware, potentially enabling point-of-care diagnostics for personalized cancer treatment. More generally, this approach could elucidate and quantify genotype-phenotype links in cancer.

Authors

  • Jakob Nikolas Kather
    Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
  • Lara R Heij
    Institute of Pathology, University Hospital RWTH Aachen, Aachen, Germany.
  • Heike I Grabsch
    Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, Netherlands.
  • Chiara Loeffler
    Department of Medicine III, University Hospital RWTH Aachen, Aa-chen, Germany.
  • Amelie Echle
    Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
  • Hannah Sophie Muti
    Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
  • Jeremias Krause
    Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
  • Jan M Niehues
    Department of Medicine III, University Hospital RWTH Aachen, Aa-chen, Germany.
  • Kai A J Sommer
    Department of Medicine III, University Hospital RWTH Aachen, Aa-chen, Germany.
  • Peter Bankhead
    MRC Institute of Genetics and Molecular Medicine, University of Ed-inburgh, Edinburgh, UK.
  • Loes F S Kooreman
    Department of Pathology, GROW School for Oncology and Develop-mental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands.
  • Jefree J Schulte
    Department of Pathology, University of Chicago Medicine, Chicago, IL, USA.
  • Nicole A Cipriani
    Department of Pathology, University of Chicago Medicine, Chicago, IL, USA.
  • Roman D Buelow
    Institute of Pathology, University Hospital RWTH Aachen, Aachen, Germany.
  • Peter Boor
    Institute of Pathology, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
  • Nadi-Na Ortiz-Brüchle
    Institute of Pathology, University Hospital RWTH Aachen, Aachen, Germany.
  • Andrew M Hanby
    Pathology & Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
  • Valerie Speirs
    Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
  • Sara Kochanny
    Department of Medicine, University of Chicago Medicine, Chicago, IL, USA.
  • Akash Patnaik
    Department of Medicine, University of Chicago Medicine, Chicago, IL, USA.
  • Andrew Srisuwananukorn
    Department of Medicine, University of Illinois - Chicago, Chicago, IL, USA.
  • Hermann Brenner
    German Cancer Consortium (DKTK), Heidelberg, Germany.
  • Michael Hoffmeister
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Piet A van den Brandt
    Department of Epidemiology, Maastricht University Medical Center+, Maastricht, The Netherlands.
  • Dirk Jäger
    Department of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
  • Christian Trautwein
    Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
  • Alexander T Pearson
    Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.
  • Tom Luedde
    Division of Gastroenterology, Hepatology and Hepatobiliary Oncology, University Hospital RWTH Aachen, Aachen, Germany.