P250 RNASeq identifies differential gene expression in colorectal and duodenal adenomas in familial adenomatous polyposis (FAP)

Published Date: 18th June 2023

Publication Authors: Fedail A

Abstract

Introduction
Familial adenomatous polyposis (FAP) is an autosomal dominant condition caused by a germline mutation in the APC gene (Campos et al., 2015). Patients develop hundreds to thousands of polyps along their intestinal tract in the second and third decades of life (Vasen et al., 2008). Without prophylactic colectomy, the lifetime risk of colorectal cancer is 100% (Campos, 2014). The cumulative incidence rate for duodenal cancer in FAP patients is 4.5% at age 57 (Bulow, 2004). The genetic causes of the discrepancies between the rate of colorectal and duodenal adenomas and cancer in FAP patients are not yet fully understood.

Methods
1. Duodenal normal mucosa (n=26), duodenal polyp biopsies (n= 26) and colorectal normal mucosa (n=36), colorectal polyp biopsies (n=36) were collected from FAP patients.

• DNA extraction from blood samples was performed using an automatic DNA extraction facility (Hamilton).
• RNA extraction from biopsies was by AllPrep kit (Qiagen).
• Whole transcriptome sequencing by RNASeq of adenomas and normal mucosa was completed by the Wales Gene Park (WGP) Genomic facility, Cardiff, UK.
• Differentially Expressed Gene analysis (DEG) was carried out using the R package ‘DESeq2’ by the WGP.
• Gene Ontology analysis using PANTHER 16.0 was used for functional annotation of genes (Ashburner et al., 2000).
• Reactome was used to visualize biological pathways (Jassal et al., 2019).

Conclusion:
Differences in expression of genes were found between duodenal and colonic adenomas in FAP. These differences extend to the pathways the genes are involved in. CDH3 was one of the highly overexpressed genes in the duodenal adenoma samples, it is involved in cell junction organization. Collagen degradation was a major pathway in colonic adenomas with MMP10 one of the most overexpressed genes. Under-expressed genes in the duodenum include GUCA2B, it is involved in digestion and absorption. Extracellular matrix organization was heavily downregulated in the colon adenoma samples with ADAMTS16 one of the notably under-expressed genes. Genes from this data could be used as biomarkers for disease progression, help further understand the genesis of the disease in both regions and identify possible target sites for therapy.

 

 

Fedail, A; Thomas, L. (2023). P250 RNASeq identifies differential gene expression in colorectal and duodenal adenomas in familial adenomatous polyposis (FAP). Gut. 72(Suppl 2), pp.A181-A182. [Online]. Available at: https://doi.org/10.1136/gutjnl-2023-BSG.318 [Accessed 15 December 2023]

 

« Back