We were studying cancer mutations in tumour suppressor proteins that lead to the expression of shortened forms of these proteins. We discovered a class of truncated proteins that unexpectedly acquired novel functions to promote the growth of cancer cells. We were keen to find out what protein interactions were involved, what kind of gene expression profiles were induced, and how these link to clinical subtypes of colorectal cancer, but we lacked the expertise to solve these issues. By sharing this work at an early stage during one of the Oncode meetings, I connected with Oncode Investigators Michiel Vermeulen (Radboud University) and Jan Paul Medema (Amsterdam University Medical Center), who are both interested in colorectal cancer. Michiel is an expert in mass-spectrometry, RNA sequencing and bioinformatics, and Jan Paul has expertise in molecular subtyping of colorectal cancer and associated clinical information. We subsequently decided to work together to solve these issues.

During our first interactions, we connected people from our labs to move the project forward. Together, we solved the mechanism by which these shortened mutant proteins operated and we discovered that their growth-promoting activity connects to a distinct patient subgroup when compared to other more common mutations that mediate deletion of the protein. Our findings also predict that patients carrying these mutations are not sensitive to novel therapies that are currently being evaluated in clinical trials. In summary, this work taught us that examining patient-derived mutations is highly relevant, not only to understand disease mechanisms but also to improve applications of precision medicine.

In my view, the best part of this collaboration was the enthusiasm and inventiveness with which the young people in our labs - Nicola Fenderico from my lab and Rik Lindeboom from Michiel’s lab - worked together to solve our research questions. This collaboration also strengthened my interactions with both Michiel and Jan Paul. In fact, it led to a new collaboration with Michiel’s group, in which we aim to solve the mode of action of a novel lead compound that my lab works on. Furthermore, Jan Paul put me in touch with a clinician at VU-AMC, with whom we are now investigating the molecular basis of a rare type of inherited colorectal cancer. This shows that one collaboration can lead to more collaborations, which not only firms up the connection between Oncode Investigators but also expands the network of the younger generation in the lab.