Particular DNA Changes Linked with Prostate Cancer Development and Lethality
Published online in Cancer, April 22
Researcher's Note, from Wennuan Liu, Ph.D.
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 tumor tissue and blood markers for prognosis, physicians still cannot tell for sure what type of prostate cancer a patient has at the timeof 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 canexamine copy number alterations in all regions of the DNA from prostate tumors, 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.
A new analysis has found that the loss or amplification of particular DNA regions contributes to the development of prostate cancer, and that patients with two of these DNA changes have a high likelihood of dying from the disease. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the study provides valuable information on the genetics of prostate cancer and offers insights into which patients should be treated aggressively.
Cells can become cancerous when they lose or amplify pieces of DNA containing important genes. Using a method that can detect these genetic changes in cells from prostate tumors from 125 patients, Jianfeng Xu, MD, DrPh, Director of Center for Cancer Genomics at the Wake Forest School of Medicine in Winston-Salem, and his colleagues at Wake Forest, Brady Urological Institute of Johns Hopkins Medical Institutions, and Karolinska Institute of Sweden found that changes in 20 gene regions likely contribute to prostate cancer development. Four of these regions had not been reported before. Importantly, changes in seven of the 20 regions were linked with early death from prostate cancer. Also, patients whose cancer cells had a loss of the PTEN gene and an amplification of the MYC gene were more than 50 times as likely to die from prostate cancer than other patients who had similarly staged tumors and prostate-specific antigen levels at the time of diagnosis. Analyses of 333 tumors from additional patients confirmed the link between PTEN and MYC and prostate cancer lethality.
In addition to providing new information about the genetic changes involved in the development and progression of prostate cancer, the findings may help guide doctors as they weigh different treatment options for patients with the disease. "For example, prostate cancer patients who have DNA copy number alterations at PTEN and MYC may not be appropriate candidates for active surveillance and should be treated intensively," explained Dr. Xu.
Article: "Genetic markers associated with early cancer-specific mortality following prostatectomy." Wennuan Liu, Chunmei C. Xie, Christopher Y. Thomas, Seong-Tae Kim, Johan Lindberg, Lars Egevad, Zhong Wang, Zheng Zhang, Jishan Sun, Jielin Sun, Patrick P. Koty, A. Karim Kader, Scott D. Cramer, G. Steve Bova, S. Lilly Zheng, Henrik Grönberg, William B. Isaacs, and Jianfeng Xu, MD, DrPh. CANCER; Published Online: April 22, 2013 (DOI: XXX/cncr.XXX).
CANCER is a peer-reviewed publication of the American Cancer Society integrating scientific information from worldwide sources for all oncologic specialties. The objective of CANCER is to provide an interdisciplinary forum for the exchange of information among oncologic disciplines concerned with the etiology and course of human cancer. CANCER is published by Wiley-Blackwell and can be accessed online at http://wileyonlinelibrary.com/journal/cancer.
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