In a first-of-its-kind study, researchers from the Wellcome Sanger Institute (UK) and Hubrecht Institute (Utrecht, The Netherlands) have utilized the latest single cell and organoid technologies to demonstrate that in bowel cancer, every tumour is different and that every cell within the tumour is also genetically unique. The research was recently published in Nature.
To investigate the nature and extent of intra-tumor diversification, the researchers characterized organoids derived from multiple single cells from three colorectal cancers as well as from adjacent normal crypts. The colorectal cells exhibited extensive mutational diversification and carried several-fold more somatic mutations than normal colorectal cells.
“Organoids had not been used to study single cancer cells before. Nobuo Sasaki in my lab isolated multiple single cells from the tumors and grew them up as organoids. This enabled us to study each cell without the errors that standard single cell methods bring. For the first time ever, we could make a really comprehensive comparison of individual normal and tumour cells from the exact same type of tissue, taken at the same time, from the same person, and see how the cancer had developed,” Hans Clevers, from Hubrecht Institute, joint corresponding author on the paper, explained.
Overall, the findings indicate that colorectal cancer cells undergo substantial increases in somatic mutation rate compared to normal colorectal cells and that genetic diversification of each cancer is accompanied by pervasive, stable and inherited differences in the biological states of individual cancer cells.
“We knew before that cancers contained subclones, but this is the first time that anyone has shown that each cell in a tumour is different,” Sophie Roerink, joint first author from the Wellcome Sanger Institute, commented.