New Molecular Characterisation of GI Tumours Pancreatic Cancer

Chapter 1 - Biology of Cancer Development in the GI Tract

Pancreatic Cancer

Somatic mutations in ataxia telangiectasia mutated (ATM) are present in significant proportions of patients (8%), highlighting the importance of BRCA-mediated DNA damage repair mechanisms in sporadic pancreatic ductal adenocarcinoma (PDAC) as well as familial disease. Mutations in genes involved in chromatin remodelling such as ARID1A, EPC1 and ARID2 are frequently observed, indicating chromatin remodelling may have an important role in PDAC.

Novel mutations in genes traditionally described for their roles in axon guidance have been observed by a combination of genomic data and supportive experimental evidence from independent murine Sleeping Beauty (SB) mutagenesis screens. Axon guidance is integral to organogenesis, regeneration, wound healing and other basic cellular processes.

The widespread genomic aberrations observed in axon guidance genes suggest they may have a role in PDAC. This observation joins mounting evidence in other cancer, including a recent report demonstrating ROBO2 mutations in liver fluke-associated cholangiocarcinoma.


Revision Questions

  1. Which genes involved in chromatin remodelling are significantly mutated in pancreatic cancer?
  2. Is BRCA-dependent DNA repair a cellular function altered by mutations in pancreatic cancer?
  3. Are genes involved in axon guidance altered in pancreatic cancer?
Last update: 07 July 2016