New Molecular Characterisation of GI Tumours Gastric Cancer

Chapter 1 - Biology of Cancer Development in the GI Tract

Gastric Cancer

Recent studies by TCGA propose a molecular classification dividing gastric cancer into four subtypes:

1. Tumours positive for EBV, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and DCD1LG2 (also known as PD-L2).

2. Microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins.

3. Genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins.

4. Tumours with CIN, which show marked aneuploidy and focal amplification of receptor tyrosine kinases.

Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies.

Revision Questions

  1. Do chromosome instability and mutations in tyrosine kinase receptors frequently co-occur in gastric cancer?
  2. Are mutations in the PIK3CA gene frequent in microsatellite unstable gastric tumours?
  3. With which molecular subtype of gastric cancer is a diffuse histology related?
Last update: 07 July 2016