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Adenomatous Polyposis Syndromes: Polymerase Proofreading-Associated Polyposis

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Hereditary Colorectal Cancer

Abstract

POLE and POLD1 encode the major subunits of polymerase ε and polymerase δ, respectively. Missense germline mutations in the exonuclease domains (EDMs) of POLE and POLD1 have been found to be a rare cause of multiple colorectal adenomas and carcinomas. This condition is known as polymerase proofreading-associated polyposis (PPAP). The EDM of POLE is also somatically mutated in ~1% of colorectal cancers (CRCs) and ~8% of endometrial cancers. In this chapter we will consider the roles of these two enzymes, germline mutations that have been identified to date and their pathogenicity, the characteristics of tumours with germline or somatic mutations, clinical characteristics of patients with PPAP and the potential use of immunotherapy in patients with mutations in the EDM of POLE.

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Author information

Authors and Affiliations

  1. Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B17 9JA, UK

    Claire Palles

  2. The Polyposis Registry, St Mark’s Hospital, Harrow, London, UK

    Andrew Latchford

  3. Department of Surgery and Cancer, Imperial College London, Harrow, London, UK

    Andrew Latchford

  4. Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL and CIBERONC, Hospitalet de Llobregat, Barcelona, Spain

    Laura Valle

Authors
  1. Claire Palles
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  2. Andrew Latchford
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  3. Laura Valle
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Corresponding authors

Correspondence to Claire Palles , Andrew Latchford or Laura Valle .

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Editors and Affiliations

  1. Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL and CIBERONC, Hospitalet de Llobregat, Barcelona, Spain

    Laura Valle

  2. University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, California, USA

    Stephen B. Gruber

  3. Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL and CIBERONC, Hospitalet de Llobregat, Barcelona, Spain

    Gabriel Capellá

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Palles, C., Latchford, A., Valle, L. (2018). Adenomatous Polyposis Syndromes: Polymerase Proofreading-Associated Polyposis. In: Valle, L., Gruber, S., Capellá, G. (eds) Hereditary Colorectal Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-74259-5_8

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