The likelihood of metastasis is a critical factor of whether to select conservative management or continued therapy for men newly diagnosed with prostate cancer or those who have already been treated. Primary tumor growth and spread are fueled by amplifications or deletions of sections of the genome known as copy number alterations (CNAs) in prostate and other cancers.
A new test for assessing CNAs has been described in The Journal of Molecular Diagnostics, and it has the potential to dramatically improve prostate cancer evaluation by being cheaper, faster, more reproducible, and requiring less tissue than previous diagnostic approaches.
Prostate cancer metastases account for about 16% of all prostate cancers and 8% of all male cancer deaths. Men at risk of metastases who would benefit from vigorous therapy can be identified with accurate prediction at the time of diagnosis.
The presence of CNAs in prostate tissue or blood can indicate if the disease that was previously diagnosed has progressed. The increased and deleted genes could be used to treat aggressive prostate cancer in the future.
“We have demonstrated that CNAs can be detected rapidly and accurately with the new Next-Generation Copy Number Alteration (NG-CNA) assay. The impact of this information is two-fold: to assure aggressive therapy at the time of diagnosis for men with metastasis-prone disease and provide a rationale for active surveillance (and not overtreatment) for men with indolent disease,” explained lead investigator Harry Ostrer, MD, of the Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
We believe the addition of the NG-CNA assay onto a standard cancer gene testing platform will augment personalized medicine by identifying aggressive tumors and genetic mutations that are predictors of response to targeted therapies.
Dr. Harry Ostrer
The NG-CNA assay is a targeted amplification sequencing method that can examine 902 genomic locations across 194 genomic regions. NG-CNA can process samples faster and at a lower cost per sample than array comparative genomic hybridization array (CGH).
“For example, with NG-CNA the cost of DNA extraction, library preparation, and sequencing reagents can be $20 to $40 per sample, compared to nearly $1000 for whole genome sequencing,” said Dr. Ostrer.
In fact, “massively multiplexed assays, like the NG-CNA assay, provide an entry into personalized medicine applications at a fraction of the cost of traditional whole-genome sequencing approaches,” added first author Viacheslav Fofanov, Ph.D., of the School of Informatics, Computing, and Cyber Systems, Northern Arizona University, Flagstaff, AZ, USA.
Another advantage of NG-CNA is that the results are easier to interpret than those obtained from whole genome sequencing. With a normal turnaround time of 36 hours, the new assay can process hundreds to thousands of samples in a single run. In addition, samples evaluated using the NG-CNA assay require less data storage than samples evaluated with whole genome sequencing.
“This allows our approach to move from large reference laboratories to smaller, more resource-constrained independent laboratories as needed,” added Dr. Ostrer.
The NG-CNA assay also has the advantage of being able to process lower amounts of material (as little as 12.5 ng) than other procedures, allowing cell lines, surgical samples, and biopsies to be evaluated. The CNA method also creates a single platform for other sequencing tests, such as companion diagnostic assays, to be added.
Using data from different assessment techniques, the researchers developed the metastatic potential score (MPS) as an indicator of metastatic potential in earlier study. The MPS was found to be strongly predictive of prostate cancer, triple-negative breast cancer, and lung adenocarcinoma metastases, according to the researchers.
The MPS was computed using NG-CNA assay data in 70 prostate cancer surgical research samples with known clinical outcomes in the current study, and the results were well correlated with those of the Oncoscan CNV assay.
Clinical and analytical validity was discovered between surgical samples and matched biopsies processed exclusively on the NG-CNA platform in a separate cohort. A MPS threshold of 0.99 distinguished high-risk tumors from low-risk ones.
“We believe the addition of the NG-CNA assay onto a standard cancer gene testing platform will augment personalized medicine by identifying aggressive tumors and genetic mutations that are predictors of response to targeted therapies,” said Dr. Ostrer.
