Results from a recent study show that large chromosomal rearrangements yield biomarkers that can identify and distinguish individuals with low versus intermediate and high risk for prostate cancer (Mayo Clinic Proceedings. 2018;94[1]:27-36).

The study was conducted by George Vasmatzis, PhD, Co-Director of the Biomarker Discovery Program within the Center for Individualized Medicine Rochester, Minnesota, and colleagues to assess whether chromosomal rearrangements can be used to distinguish low risk from intermediate and high risk prostate cancer, and to determine if these rearrangements can help pinpoint men with low risk for prostate cancer who harbor intermediate and high risk prostate cancer in the prostate gland.

Between August 14, 2001, and July 15, 2011, Dr Vasmatzis and colleagues obtained 154 frozen specimens from 126 patients and detected chromosomal rearrangements by carrying out mate pair sequencing of amplified DNA from pure populations of Gleason patterns in the specimens. This led to the identification of biomarkers for potential chromosomal rearrangements with higher incidence in intermediate and high versus low risk for prostate cancer.

In addition, the investigators performed an independent validation using fluorescence in situ hybridization on 152 specimens obtained from 124 patients between February 12, 2002, and July 12, 2008.

Ultimately, they found that the number of abnormal junctions did not distinguish low from intermediate and high risk for progression to prostate cancer. Of note, loci corresponding with genes implicated in prostate cancer had higher rates of alteration in intermediate and high risk prostate cancer.

A total of 6 potential markers were produced from integrated analysis of copy number variations and microarray data; according to Dr Wang and colleagues, these markers were more frequently detected in Gleason pattern [GP]3 of a Gleason score[GS]7 of prostate cancer than in GP3 of a GS6 prostate cancer.

Using an independent sample set with statistically significant areas under the receiver operating characteristic curves (AUCs), they cross-validated 5 of the potential markers. Probes detecting gains in ASAP1, MYC, and HDAC9 had respective AUCs of 0.71 (95% confidence interval [CI], 0.59-0.84), 0.82 (95% CI, 0.71-0.93), and 0.77 (95% CI, 0.66-0.89), and probes detecting deletions in PTEN and CHD1 had AUCs of 0.87 (95% CI, 0.77-0.97) and 0.73 (95% CI, 0.60-0.86), respectively.

“We have developed a discovery and validation process for the identification of genomic abnormalities of LRP and IHRP [low risk progression and intermediate and high risk progression] to PCas [prostate cancers]. Fluorescence in situ hybridization probes for deletions in PTEN and CHD1 and gains in ASAP1, HDAC9, and MYC highly distinguished GP3 in GS6 cancer from GP3 in GS7 cancer,” Dr Vasmatzis and colleagues said.

“Even though a number of previous reports have implicated these genes in PCa progression, our study is the first to describe the potential of this specific panel of CRs [chromosomal rearrangements] to address a critical need for the care of patients with PCa. Assays based on these probes hold promise for the risk evaluation of men with GS6 in the prostate needle biopsy specimen,” they concluded.—Hina Khaliq