Genetic abnormalities in benign or malignant tissues predict relapse of prostate cancer
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."
Provided by Elsevier
- Early warning: PSA testing can predict advanced prostate cancer Feb 15, 2008 | not rated yet | 0
- Inflammation marker may guide prognosis for prostate cancer Sep 28, 2011 | not rated yet | 0
- New prostate cancer test gives more accurate diagnosis Apr 06, 2011 | not rated yet | 0
- Novel test following prostate surgery could detect cancer recurrence earlier Sep 29, 2010 | not rated yet | 0
- When rising PSA means prostate cancer is in patient's future May 18, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
4 hours ago From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
20 hours ago I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
(HealthDay)—Concurrent use of two immune checkpoint antibodies—ipilimumab and nivolumab—may be effective for the treatment of advanced melanoma, according to a proof-of-principal study presented in ...
Cancer 16 hours ago | not rated yet | 0
(HealthDay)—The risks of metastasis and death associated with cutaneous squamous cell carcinoma (CSCC) are low, but significant, and risk factors for poor outcome include tumor diameter, invasion beyond ...
Cancer 16 hours ago | not rated yet | 0 |
A new review finds cancer survivors suffer a diverse and complex set of impairments, affecting virtually every organ system. Writing in CA: A Cancer Journal for Clinicians, Julie Silver, M.D., associate professor at Harvar ...
Cancer 21 hours ago | not rated yet | 0
(AP)—A California doctor has been sentenced to 14 years in federal prison for bilking her patients out of more than $1 million by promising that an herbal supplement could cure late-stage cancer and other diseases.
Cancer 21 hours ago | not rated yet | 0
A new oral targeted drug, idelalisib (GS-1101), has the potential to stave off the need for additional treatments for relapsed or treatment-resistant chronic lymphocytic leukemia (CLL), according to a study led in part by ...
Cancer 23 hours ago | not rated yet | 0 |
Big names in medicine are set to give an upbeat assessment of the war on AIDS on Tuesday, 30 years after French researchers identified the virus that causes the disease.
5 hours ago | not rated yet | 0
For combat veterans suffering from post-traumatic stress disorder, 'fear circuitry' in the brain never rests
Chronic trauma can inflict lasting damage to brain regions associated with fear and anxiety. Previous imaging studies of people with post-traumatic stress disorder, or PTSD, have shown that these brain regions can over-or ...
6 hours ago | not rated yet | 0 |
(Medical Xpress)—What if the quality of your work depends more on your focus on the piano keys or canvas or laptop than your musical or painting or computing skills? If target users can be convinced, they ...
18 hours ago | 3.7 / 5 (3) | 0 |
The neural machinery underlying our olfactory sense continues to be an enigma for neuroscience. A recent review in Neuron seeks to expand traditional ideas about how neurons in the olfactory bulb might encode information about ...
17 hours ago | not rated yet | 0 |
In 2008 researchers from the University of Southern Denmark showed that the drug thioridazine, which has previously been used to treat schizophrenia, is also a powerful weapon against antibiotic-resistant bacteria such as ...
15 hours ago | 3.7 / 5 (3) | 0 |
Treatment for alcohol use disorders works best if the patient actively understands and incorporates the interventions provided in the clinic. Multiple factors can influence both the type and degree of neurocognitive abnormalities ...
15 hours ago | not rated yet | 0 |