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A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer
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Consensus molecular subtype classification of colorectal adenomas.

Malgorzata A Komor1,2, Linda Jw Bosch1, Gergana Bounova3

  • 1Translational Gastrointestinal Oncology, Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

The Journal of Pathology
|July 4, 2018
PubMed
Summary

Colorectal adenomas can be classified into consensus molecular subtypes (CMS), with CMS3 being most common. CMS1 and CMS2 subtypes may indicate adenomas with higher risk of progressing to colorectal cancer.

Keywords:
adenomacoloncolorectal cancerneoplasiarectum

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Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • Colorectal cancer (CRC) develops from adenomas, with only a subset progressing to malignancy.
  • Genomic alterations during CRC pathogenesis influence RNA expression.
  • Consensus molecular subtyping (CMS) is an RNA expression-based classification for CRC.

Purpose of the Study:

  • To determine if colorectal adenomas can be stratified into CMS classes.
  • To investigate the relationship between CMS classes in adenomas and DNA copy number aberrations associated with malignant progression.

Main Methods:

  • RNA sequencing of 62 adenomas and 59 CRCs.
  • Microsatellite instability (MSI) determination via PCR.
  • DNA copy number assessment using low-coverage sequencing or array-comparative genomic hybridization.
  • Adenoma and CRC classification into CMS using an established classifier, including data from The Cancer Genome Atlas.

Main Results:

  • 87% of adenomas (54/62) were successfully classified into CMS.
  • CMS3 (metabolic subtype) was most prevalent in adenomas (73%), while least common in CRCs.
  • CMS1 (MSI immune) was found in 2% of adenomas (one of two MSI-positive cases).
  • CMS2 (canonical) was identified in 13% of adenomas.
  • No adenomas were classified as CMS4 (mesenchymal).
  • CMS3 enriched low-risk adenomas; CMS2 showed a higher proportion of high-risk adenomas.

Conclusions:

  • Colorectal adenomas can be stratified into consensus molecular subtypes (CMS).
  • CMS1 and CMS2 expression signatures may identify adenomas with an increased risk of progression to CRC.
  • The observed CMS distribution in adenomas aligns with the expected progression rates to colorectal cancer.