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  • Review Article
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Molecular subtypes in cancers of the gastrointestinal tract

Nature Reviews Gastroenterology & Hepatology volume 14, pages 333–342 (2017)Cite this article

Subjects

Key Points

  • The advent of affordable genomic and transcriptomic methods has enabled the identification of distinct molecular entities in nearly all gastrointestinal cancers

  • These molecular subtypes capture complex phenotypic variation in a limited number of definable brackets with biological and clinical pertinence

  • Molecular subtypes are highly interconnected across various gastrointestinal cancers and many of these subtypes can be identified regardless of organ of origin

  • In colorectal cancers, consensus subtypes have been defined and these could serve as a platform for similar efforts across other gastrointestinal cancers

Abstract

Malignancies of the gastrointestinal tract are among the most common human cancers. The distinct tissues of origin give rise to a diverse set of diseases, such as colorectal cancer, pancreatic carcinoma and gastric cancers, with each associating with specific clinical features. Genomic and transcriptomic analyses have further defined the heterogeneity that occurs within these cancers by identifying so-called molecular subtypes. These subtypes are characterized by specific genetic aberrations and expression signatures that suggest important biological differences. Although at first sight this subdivision of organ-specific cancers might increase the complexity of classification, closer analysis suggests that the subtypes detected in the various malignancies are recurring. For example, nearly all gastrointestinal cancers appear to present with subtypes that are either characterized by a mesenchymal gene expression signatures, extensive immune infiltration or metabolic dysregulation. Additionally, in each of the gastrointestinal malignancies, a 'canonical' subtype is recognized that retains characteristic features of the epithelial tissue of origin. These common themes can enhance our collective understanding of these malignancies, and could perhaps be therapeutically exploited. In this Review, the identification of subtypes in the various gastrointestinal cancer types are discussed along with how they could be incorporated into clinical practice.

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Figure 1: Complexity of gastrointestinal cancer classification.
Figure 2: Two hypothetical scenarios for the origin of molecular subtypes.

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Acknowledgements

This work was supported by grants from The Dutch Cancer Foundation (KWF; UVA2014-7245), the European Research Council (ERG-StG 638193) and The Netherlands Organisation for Health Research and Development (ZonMw; Vidi 016.156.308) to L.V, and KWF (UVA2012-6507) to M.F.B. A.S. acknowledges NHS funding to the National Institute for Health Research's Biomedical Research Centre at The Royal Marsden, London UK, and the Institute of Cancer Research. P.T. acknowledges funding from National Medical Research Council grants in Singapore (TCR/009-NUHS/2013 and NMRC/STaR/0026/2015).

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  1. Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands

    Maarten F. Bijlsma & Louis Vermeulen

  2. Division of Molecular Pathology, The Institute of Cancer Research, 15 Cotswold Road, London, SM2 5NG, UK

    Anguraj Sadanandam

  3. Cancer and Stem Cell Biology Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.,

    Patrick Tan

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Correspondence to Louis Vermeulen.

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A.S. is entitled to a share of royalties received by the licensor for a patent entitled 'Colorectal cancer classification with differential prognosis and personalized therapeutic responses'; patent number PCT/IB2013/060416. M.F.B. has received research funding from Celgene, and A.S. from Bristol-Myers Squibb. P.T. holds patents covering gene expression classifiers for gastric cancer. These parties were not involved in drafting of the manuscript.

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Bijlsma, M., Sadanandam, A., Tan, P. et al. Molecular subtypes in cancers of the gastrointestinal tract. Nat Rev Gastroenterol Hepatol 14, 333–342 (2017). https://doi.org/10.1038/nrgastro.2017.33

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