Patient-derived organoids from normal and tumoral colorectal tissue

Abstract

Colon and rectum are part of the same organ but have different embryological, anatomical and physiological characteristics. Although cancers from these two regions are often referred to as “colorectal cancer or CRC”, colon and rectal tumors differ in risk factors and mutational landscapes, which are analysed from complex heterotypic tumor biopsies. Accordingly, patients with colon or rectal tumors are managed differently in the clinic. Organoid technology allows the isolation and culture of normal and tumor stem cells, giving rise to structures that resemble functions and architecture of origin tissue or tumor. To gain further insight the transcriptomic and functional differences between colon and rectal cancers, we have generated two living biobank of 3D organoid cultures derived from human epithelial stem cells: a) the colon biobank from matched normal and tumor surgical samples of colon cancer patients; and b) a rectum biobank from endoscopy samples of normal rectum and rectal tumors, and when possible also from normal colon tissue, of rectal cancer patients. Endoscopy biopsies were obtained at diagnosis and so, they had never been exposed to radio- or chemotherapy. The study of functional behaviour and gene expression profiles of organoid cultures from colon and rectum will allow us to understand the possible differences between these two tissues in normal and tumoral conditions.