Other than skin cancer, prostate cancer is the most common cancer in men in the western world. About 1 man in 9 will be diagnosed with prostate cancer during his lifetime. About 6 cases in 10 are diagnosed in men aged 65 or older, and it is rare before age 40.
While diagnosing prostate cancer, one of the key challenges is to determine between aggressive and non-aggressive disease. To solve this challenge, an international team of scientists at the German Cancer Research Center (DKFZ) studied the earliest mutational events in prostate cancer to develop a computer model.
For the study, scientists collected patient information from near 300 men who have had their whole cancer genome sequenced to describe all changes present in the tumor. Enlighting data set, the analysts have built up the computer model which can be utilized to foresee how a prostate cancer will produce for a given patient.
The computer model is being implemented at a clinic in Germany. The researchers expect it to take two to three years to have the model fully implemented as an integral part of the clinic’s processes. Later, in a not too distant future, the researchers hope that the model can also be introduced at hospitals in other countries, for example, Denmark.
Co-author of the study Joachim Weischenfeldt, BRIC, UCPH said, “If we have a patient with a particular set of mutations, we can use the model to predict the most likely next mutation that the patient will experience at some point – and how it will affect the patient’s clinical situation. As an illustration, we can predict with some probability that if you have mutation A, you are likely to get mutation B before you get C. We can also predict if the next mutation is likely to change the clinical outcome of the disease.”
“So far, our data sets comprise around 300 patients, but we expect to collect data from several thousand patients in the coming years. The model will be better the more data it can learn from.”
Almost 300 patients from the study had their entire genome sequenced. With genome sequencing, it becomes conceivable to tailor the treatment of the individual – also alluded to as customized medication.
The patients whose information the scientists have utilized have principally been purported early beginning patients. This gathering is characterized as men who are determined to have prostate cancer before achieving the age of 55 years.
Co-author Doctor Clarissa Gerhauser, DKFZ said, “Prostate cancer develops over many years. We have therefore been particularly interested in the group of patients where the cancer is detected at a young age as this allows us to analyze the tumor at an early stage. This is an important element because in this way we get a clearer picture of the first mutations and alterations that occur in the tumor, to find out what is the initiating factor.”
However, it was not been known precisely what initiates prostate cancer. However, due to the focus on the earliest detected tumors, scientists analyzed a mutational mechanism involving an enzyme called APOBEC. This enzyme may help trigger the disease – i.e. trigger some of the very first mutations in prostate cancer.
Co-author Doctor Jan O. Korbel, group leader at EMBL said, “We hypothesize that this enzyme mutates the prostate cells at a low but constant rate. Each time the cell divides, APOBEC is likely to cause mutations. If you have early-onset prostate cancer, you may have a couple of mutations caused by APOBEC. Twenty years later, you may have 10-20 mutations.”
Joachim Weischenfeldt said, “The most common oncogene in prostate cancer involves a certain fusion gene. The APOBEC enzyme may contribute to the formation of this fusion gene. We cannot say that there is causality, but there is a strong correlation between mutations caused by APOBEC and other alterations such as this fusion gene.”
The specialists have likewise discovered a putative novel oncogene in prostate cancer growth – ESRP1 – which is related to quick isolating and exceptionally forceful prostate cancer. It is found intently to a definitely known oncogene.
According to scientists, this is the reason that has not been discovered until now. Through this study, scientists show that the oncogene ESRP1 may be used as a possible new biomarker to detect whether a patient will have aggressive prostate cancer, which they validated on a cohort consisting of 12,000 other patients with the same type of cancer.
The study is the result of a large transnational collaboration between universities from different countries among others Germany, Norway, Canada and Denmark. Besides UCPH, DKFZ, EMBL, Max Planck Institute for Molecular Genetics and Charité – Universitätsmedizin Berlin has e.g. also been involved with professor and co-author Thorsten Schlomm, who is leading the clinical implementation of the computer model at the clinic in Germany.
Scientists have published their story in the journal Cancer Cell.