Researchers made 665 patient-derived tumor models available and compared them with the source tissue

Researchers made 665 patient-derived tumor models available and compared them with the source tissue

An international program assembled 665 tumor models grown from patient tissue across 25 cancer types. In an article published on 5 August, the authors compared the models with the source tissue and made both the models and the data available to other laboratories.

Patient-derived models are cell cultures grown from tumor tissue. They include three-dimensional organoids and spheroids, as well as cell lines. Researchers use them to identify genes on which tumor cells depend and to test drugs. However, cells outside the body live in a different environment and may lose or alter some properties of the original tumor. Before conducting an experiment, researchers therefore need to know which properties the culture has retained.

The authors compared key DNA features in 421 matched pairs of patient tumors and derived cultures. At least two of the four assessed features were preserved in 97,8% of the models. These features included mutations and the number of copies of specific DNA regions. The authors also examined methylation in another 201 pairs. Methylation consists of chemical marks on DNA that help regulate gene activity. In 190 of these pairs (95%), the culture's methylation profile was more similar to that of its own tumor than would be expected from a random match.

Cell state was more sensitive to culture conditions. The set of active genes changed in some cultures. In one glioblastoma model, derived from an aggressive brain tumor, changing the medium in which the cells grew altered this set of genes. Culture conditions therefore need to be considered when planning an experiment because they can change the state of the cells.

Detailed clinical information is available for 522 models. Combined with the molecular data, this information can help a researcher studying tumor resistance to treatment select a culture based on its genome, the patient's history, and the culture conditions. The choice of model can then be justified because the researcher can see which aspects of the original tumor's biology have already been compared with the culture.