Every Bowel Tumor Has a Unique Genetic Blueprint

In the first study of its kind, a research team used the latest single cell and organoid technologies to study the mutational processes of cancer cells. The study on bowel cancers shows that not only is every tumor different but every cancer cell has a unique genetic pattern. The study from the Wellcome Sanger Institute, UK and Hubrecht Institute (KNAW) in Utrecht, The Netherlands is published in Nature.

Study Overview

The study worked with Colorectal Cancer tissues from three different patients. The tissues were collected from the normal bowel stem cells and cells from four different areas of the tumors. The tissues were then grown into organoids, 3D mini-guts, in the laboratory to amplify a single cell.

While it is known that cancers contain subclones, this is the first time that anyone has shown that each cell in a tumor is different.

Prof Hans Clevers, from Hubrecht Institute in the Netherlands, the joint corresponding author on the paper, said: "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 tumor cells from the exact same type of tissue, taken at the same time, from the same person, and see how the cancer had developed."

Study Highlights

• Every tumor is different, and every cell within the tumor is also genetically unique.
• Mutational process in tumor cells is more than normal cells, leading to a huge increase in mutation rate for tumors compared with normal cells.
• The high mutation rate may be responsible for the high genetic diversity within the tumors.
• The mutation rate starts to change many years before the diagnosis of the cancer. This time window may provide diagnostic clues in the future, if it were possible to identify the rise in mutation rate early in a cell.

Prof Sir Mike Stratton, the joint corresponding author on the paper from the Wellcome Sanger Institute, said: "This study gives us fundamental knowledge on the way cancers arise. By studying the patterns of mutations from individual healthy and tumor cells, we can learn what mutational processes have occurred, and then look to see what has caused them. Extending our knowledge on the origin of these processes could help us discover new risk factors to reduce the incidence of cancer, and could also put us in a better position to create drugs to target cancer-specific mutational processes directly."

Source-Medindia