[New molecular classification of colorectal cancer, pancreatic cancer and stomach cancer: Towards "à la carte" treatment?]

Bull Cancer. 2016 Jul-Aug;103(7-8):643-50. doi: 10.1016/j.bulcan.2016.05.007. Epub 2016 Jun 23.
[Article in French]

Abstract

This review reports 3 of recently published molecular classifications of the 3 main gastro-intestinal cancers: gastric, pancreatic and colorectal adenocarcinoma. In colorectal adenocarcinoma, 6 independent classifications were combined to finally hold 4 molecular sub-groups, Consensus Molecular Subtypes (CMS 1-4), linked to various clinical, molecular and survival data. CMS1 (14% MSI with immune activation); CMS2 (37%: canonical with epithelial differentiation and activation of the WNT/MYC pathway); CMS3 (13% metabolic with epithelial differentiation and RAS mutation); CMS4 (23%: mesenchymal with activation of TGFβ pathway and angiogenesis with stromal invasion). In gastric adenocarcinoma, 4 groups were established: subtype "EBV" (9%, high frequency of PIK3CA mutations, hypermetylation and amplification of JAK2, PD-L1 and PD-L2), subtype "MSI" (22%, high rate of mutation), subtype "genomically stable tumor" (20%, diffuse histology type and mutations of RAS and genes encoding integrins and adhesion proteins including CDH1) and subtype "tumors with chromosomal instability" (50%, intestinal type, aneuploidy and receptor tyrosine kinase amplification). In pancreatic adenocarcinomas, a classification in four sub-groups has been proposed, stable subtype (20%, aneuploidy), locally rearranged subtype (30%, focal event on one or two chromosoms), scattered subtype (36%,<200 structural variation events), and unstable subtype (14%,>200 structural variation events, defects in DNA maintenance). Although currently away from the care of patients, these classifications open the way to "à la carte" treatment depending on molecular biology.

Keywords: Adénocarcinome colorectal; Classification moléculaire; Colorectal cancer; Gastrique et pancréatique; Molecular classification; Pancreatic cancer; Stomach cancer.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma / classification
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Class I Phosphatidylinositol 3-Kinases
  • Colorectal Neoplasms / classification
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Genes, myc
  • Genes, ras
  • Humans
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism
  • Mutation
  • Pancreatic Neoplasms / classification
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / mortality
  • Phosphatidylinositol 3-Kinases / genetics
  • Programmed Cell Death 1 Ligand 2 Protein / genetics
  • Programmed Cell Death 1 Ligand 2 Protein / metabolism
  • Stomach Neoplasms / classification
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Transcriptional Activation
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism

Substances

  • B7-H1 Antigen
  • Cell Adhesion Molecules
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein
  • Transforming Growth Factor beta
  • Wnt Proteins
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • JAK2 protein, human
  • Janus Kinase 2