Describe the main findings from your paper: In collaboration with Dr. William Foulkes鈥� research team and other researchers, our study identified and characterized two novel mutations in the cell cycle gene CDC20 found in families with rare ovarian cancers. The cell cycle is almost always dysregulated in human cancer, however, mutations in genes that are involved in mitosis (an important stage of the cell cycle where chromosomes are segregated in preparation for cell division) are rare. CDC20 is a protein that is heavily involved in mitotic progression. Using several model systems (patient samples, cells, yeast, and mice), we demonstrated that these CDC20 mutations are indeed linked to cancer.
What do you think makes this paper stand out from other papers in the field? CDC20 is an essential protein in mitosis and cell division, you cannot live without it. It is often overexpressed in cancer, meaning that there is a greater abundance of CDC20 in cancer than in normal conditions, and it can also be mutated in tumours. What is most exciting about our study is that we are the first to identify germline CDC20 mutations in families with histories of cancer. These mutations are not only in the tumours but are also found in the normal cells of these patients (such as skin and blood). By germline, they are passed down from one generation to another, and carriers of these mutations develop cancer.
What is your favourite experiment in this paper? I did a lot of live-cell imaging experiments, where I looked at the behaviour of these CDC20 mutants as they progressed through the cell cycle, notably during the mitosis phase. I would set up my cells for the experiment, put them under the microscope, and program it to take a series of pictures over the course of a couple days. These pictures are compiled into videos and analyzed to compare CDC20 mutant cells with normal cells. We performed these experiments on patient samples, human cell lines, and cells from our mouse model. In cell cycle research, these experiments are very robust in providing a lot of visual and statistical data to answer hypotheses. However, analysis requires a lot of work to obtain statistically significant results. Fortunately, I had many helping hands in the lab to analyze numerous individual cells from many videos.
How do you think your lab, or other researchers, could expand on this work? The simple answer would be to find more families carrying CDC20 mutations to give further support to the notion that CDC20 is a cancer susceptibility gene. This is very difficult as we have only seen them in families with these very rare cancers so far. However, with the findings of our study, researchers are now better informed that CDC20 can affect cancer initiation and progression in certain contexts.
In what ways did working on this project help you grow as a scientist? I discovered that research progress thrives on collaboration and interdisciplinarity. The success of my project is the result of a fruitful collaboration between researchers in cancer genetics and molecular cancer biology. As the lead author of this paper, I have learned a lot by synthesizing the clinical and genetics data from our collaborators with my own data from our functional and biochemical experiments. I also learned that research that is done properly takes a lot of time. I started this project during my master鈥檚, and it is certainly gratifying to see it come to such a great close. This is something that I will always bear in mind as I continue with my future research projects.
Congratulations to Owen and to all researchers involved in this project for their hard work and for this exciting publication!听.
Chen OJ, Castellsagu茅 E, Moustafa-Kamal M, Nadaf J, Rivera B, Fahiminiya S, Wang Y, Gamache I, Pacifico C, Jiang L, Carrot-Zhang J, Witkowski L, Berghuis AM, Sch枚nberger S, Schneider D, Hillmer M, Bens S, Siebert R, Stewart CJR, Zhang Z, Chao WCH, Greenwood CMT, Barford D, Tischkowitz M, Majewski J, Foulkes WD, Teodoro JG. Germline Missense Variants in CDC20 Result in Aberrant Mitotic Progression and Familial Cancer. Cancer Res. 2022 Oct 4;82(19):3499-3515. doi: 10.1158/0008-5472.CAN-21-3956. PMID: 35913887.