While active monitoring of serum prostate specific antigen (PSA) levels in men over 50 has greatly improved early detection of prostate cancer, prediction of clinical outcomes after diagnosis remains a major challenge.
Researchers from the University of Pittsburgh School of Medicine have found that a genetic abnormality known as copy number variation (CNV) in prostate cancer tumors, as well as in the benign prostate tissues adjacent to the tumor and in the blood of patients with prostate cancer, can predict whether a patient will experience a relapse, and the nature of the relapse — aggressive or indolent. Their report is published in the June issue of The American Journal of Pathology.
Copy number variations are large areas of the genome with either duplicated or missing sections of DNA. "Our analysis indicates that CNV occurred in both cancer and non-cancer tissues, and CNV of these tissues predicts prostate cancer progression," says lead investigator Jian-Hua Luo, MD, PhD, associate professor in the Divisions of Molecular and Cellular Pathology, and Anatomic Molecular Pathology, Department of Pathology, University of Pittsburgh School of Medicine. "Prediction models of prostate cancer relapse, or of the rate of PSA level increase after surgery, were generated from specific CNV patterns in tumor or benign prostate tissues adjacent to cancer samples."
To detect the abnormalities, scientists conducted a comprehensive genome analysis on 238 samples obtained from men undergoing radical prostatectomy: 104 prostate tumor samples, 85 blood samples from patients with prostate cancer, and 49 samples of benign prostate tissues adjacent to a tumor. A third of the samples were from patients exhibiting recurrence with a PSA level increasing at a rapid rate, doubling in less than four months (rapid increases are associated with lethal prostate cancer); a third from patients exhibiting recurrence with a PSA level increasing at a slow rate, doubling time greater than 15 months; and a third with no relapse more than five years after surgery. Three commercially available prostate cancer cell lines were also tested to validate the results.
Deletions of large segments of specific chromosomes occurred with high frequency, whereas amplification of other chromosomes occurred in only a subset of prostate cancer samples. Similar amplification and deletion of the same regions also occurred in benign prostate tissue samples adjacent to the cancer. Prostate cancer patients' blood was found to contain significant CNVs. Most were not unique and overlapped with those of prostate cancer samples.
Using gene-specific CNV from tumor, the model correctly predicted 73% of cases for relapse and 75% of cases for short PSA doubling time. The CNV model from tissue adjacent to the prostate tumor correctly predicted 67% of cases for relapse and 77% of cases for short PSA doubling time. Using median-size CNV from blood, the genome model correctly predicted 81% of the cases for relapse and 69% of the cases for short PSA doubling time.
Dr. Luo notes that there are several potential clinical applications using CNV tests. "For a patient diagnosed with prostate cancer, CNV analysis done on blood or normal tissues would eliminate the need for additional invasive procedures to decide a treatment mode. For a patient already having a radical prostatectomy, CNV analysis on the tumor or blood sample may help to decide whether additional treatment is warranted to prevent relapse. Despite some limitations, including the need for high quality genome DNA, CNV analysis on the genome of blood, normal prostate, or tumor tissues holds promise to become a more efficient and accurate way to predict the behavior of prostate cancer."
David Sampson | EurekAlert!
How to construct a protein factory
19.09.2019 | Universität Bern
Quality Control in Cells
19.09.2019 | Universität Heidelberg
To process information, photons must interact. However, these tiny packets of light want nothing to do with each other, each passing by without altering the...
Researchers from the Department of Atomically Resolved Dynamics of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg, the University of Hamburg and the European Molecular Biology Laboratory (EMBL) outstation in the city have developed a new method to watch biomolecules at work. This method dramatically simplifies starting enzymatic reactions by mixing a cocktail of small amounts of liquids with protein crystals. Determination of the protein structures at different times after mixing can be assembled into a time-lapse sequence that shows the molecular foundations of biology.
The functions of biomolecules are determined by their motions and structural changes. Yet it is a formidable challenge to understand these dynamic motions.
At the International Symposium on Automotive Lighting 2019 (ISAL) in Darmstadt from September 23 to 25, 2019, the Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, a provider of research and development services in the field of organic electronics, will present OLED light strips of any length with additional functionalities for the first time at booth no. 37.
Almost everyone is familiar with light strips for interior design. LED strips are available by the metre in DIY stores around the corner and are just as often...
Later during this century, around 2060, a paradigm shift in global energy consumption is expected: we will spend more energy for cooling than for heating....
Researchers from the Department of Atomically Resolved Dynamics of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg, the University of Potsdam (both in Germany) and the University of Toronto (Canada) have pieced together a detailed time-lapse movie revealing all the major steps during the catalytic cycle of an enzyme. Surprisingly, the communication between the protein units is accomplished via a water-network akin to a string telephone. This communication is aligned with a ‘breathing’ motion, that is the expansion and contraction of the protein.
This time-lapse sequence of structures reveals dynamic motions as a fundamental element in the molecular foundations of biology.
19.09.2019 | Event News
10.09.2019 | Event News
04.09.2019 | Event News
19.09.2019 | Power and Electrical Engineering
19.09.2019 | Physics and Astronomy
19.09.2019 | Event News