Particular DNA changes linked with prostate cancer development and lethality

Prostate Cancer (PCa) is the most common cancer among men in the United States. It is not clear why some prostate cancers are so ‘aggressive’ and eventually become deadly, while others remain inactive or ‘indolent’for many years. Scientists have been trying to find markers that can distinguish aggressive from indolent forms of prostate cancer. Although a lot of progress has been made in using tumour tissue and blood markers for prognosis, physicians still cannot tell for sure what type of prostate cancer a patient has at the time of diagnosis or surgery based on these markers. Many patients end up with over-treatment and unnecessary physical and mental distress. On the other hand, some patients with aggressive prostate cancer may end up with under-treatment and therefore die from this disease due to the lack of knowledge regarding the cause and also because of limited tools for prognosis. Therefore, it is extremely important to distinguish the aggressive prostate cancers from the ones that are not life-threatening or those that do not even need treatment.
From many years of research, we know that cancer cells lose and amplify many pieces of DNA containing important genes; these losses and amplifications are called DNA copy number alterations. Using a method that can examine copy number alterations in all regions of the DNA from prostate tumours, we found a total 20 regions, with 4 of them not previously reported, that likely contribute to prostate cancer development. More importantly, seven of these 20 regions were associated with early death due to prostate cancer. In addition, patients whose cancer cells had a loss of the PTEN gene and a copy number gain of the MYC gene were more likely to die from prostate cancer at an early stage after surgery than the patients who did not have copy number alterations at these two genes. Our findings from this retrospective study may allow for more accurate prognosis of patients with high-riskPCa, at the time of surgery or biopsy, and may help guide the selection of appropriate therapy once validated in prospective studies. In addition, the information generated by our study may impact clinical management or the stratification of patients in clinical trials. Wake Forest Baptist Medical Center