GENGISCAN: GENomic profiling of Gastrointestinal Inflammatory-Sensitive CANcers

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Partners:

Funding: FNRS PDR

Duration: 2014-2019

Project Overview: Gastro-intestinal (GI) cancers represent the major cause of cancer-related death worldwide. GI inflammatory diseases such as inflammatory bowel disease (IBD), chronic hepatitis/liver cirrhosis (CH/LC) and chronic pancreatitis (CP) may lead to GI cancers in a significant proportion of patients. Carcinogenesis-related chronic inflammatory disease, that follows the inflammation-dysplasia-cancer (IDC) sequence, results from slow and progressive genetic/genomic alterations specific to inflammation and is different from the carcinogenesis of sporadic cancers, that is more dependent on environmental factors.

Project Objectives:

  1. Study the genetics/genomic somatic alterations that take place over time in GI inflammatory diseases during the initiation, promotion, and transformation into cancer. State-of-the-art next generation sequencing techniques, including whole exome sequencing and gene expression profiling within a new integrative bioinformatics approach (IB)2 (ULB/VUB) will be conducted on all stages of the IDC sequence in patients suffering from IBD, CH/LC, and CP. Subtracting the genetic variation of a non-cancerous genome (germline DNA and somatic DNA from normal tissue) from the somatic DNA of the IDC counterpart may allow us to identify new IDC-specific signaling pathways that drive the IDC sequence.
  2. Development of genomic signatures to better survey patients with inflammatory diseases at risk of cancer and select patients with poor prognoses who may require more aggressive treatment. This project will involve a large clinical database and biobank (collected in the past 10 years, with more than 5000 patients enrolled at the current time).
  3. Development of new pharmaceutical targets for inflammation-driven GI cancers. This project is a unique translational platform in Belgium (ULB, ULG, and VUB) that may lead to the development of new pharmaceutical targets for inflammation-driven GI cancers.