Lynch syndrome - cancer pathways, heterogeneity and immune escape

J Pathol. 2018 Oct;246(2):129-133. doi: 10.1002/path.5139. Epub 2018 Aug 27.

Abstract

Recent work has provided evidence for genetic and molecular heterogeneity in colorectal cancers (CRCs) arising in patients with Lynch syndrome (LS), dividing these into two groups: G1 and G2. In terms of mutation and gene expression profile, G1 CRCs bear resemblance to sporadic CRCs with microsatellite instability (MSI), whereas G2 CRCs are more similar to microsatellite-stable CRCs. Here we review the current state of knowledge on pathways of precursor progression to CRC in LS and how these might tie in with the new findings. Immunotherapies are an active field of research for MSI cancers and their potential use for cancer therapy for both sporadic and LS MSI cancers is discussed. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Keywords: DNA mismatch repair; Lynch syndrome; colorectal cancer; immune escape; microsatellite instability.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / immunology*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology
  • Colorectal Neoplasms, Hereditary Nonpolyposis / therapy
  • Genetic Heterogeneity*
  • Genetic Predisposition to Disease
  • Humans
  • Microsatellite Instability*
  • Mutation*
  • Phenotype
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Transcriptome
  • Tumor Escape / genetics*

Substances

  • Biomarkers, Tumor