Common Genetic Fusion Event May Be Associated With Low-Risk Prostate Cancer

November 10, 2017

PHILADELPHIA -- November 10, 2017 -- Establishing the way in which a TMPRSS2-ERG gene fusion forms in a prostate cancer, rather than the presence of the gene fusion itself, could help identify patients with prostate cancer with a low risk of spreading, which might determine the best course of treatment for the patient, according to a study published in Cancer Research.

Active surveillance is a common approach to caring for patients with prostate cancer with a Gleason score of 6. Identifying a biomarker that, in addition to Gleason score, distinguishes men at increased risk for disease progression from those whose prostate cancer never becomes a clinically significant problem could help improve patient care, explained John C. Cheville, MD, Mayo Clinic, Rochester, Minnesota.

To look for genetic biomarkers of clinically significant or insignificant disease, the researchers used whole-genome mate pair sequencing to study gene fusions in prostate cancer tissue samples obtained from 133 patients who underwent a radical prostatectomy at the Mayo Clinic.

The prostate cancers were divided into 4 groups: 53 low-volume Gleason 6 tumours were classed as very low risk for progression, 26 high-volume Gleason 6 tumours were classed as low risk for progression, 29 Gleason 7 tumours were classed as intermediate risk for progression, and 25 Gleason 8 or higher tumours were classed as high risk for progression.

The researchers detected TMPRSS2-ERG fusions in 45% of the prostate cancers analysed, which is consistent with prior studies, according to Dr. Cheville. Fusions were detected in 43%, 49%, 52%, and 24% in the very-low risk, low-risk, intermediate-risk, and high-risk groups, respectively.

Among the 60 prostate cancers with TMPRSS2-ERG fusions, 39 had deleted the interstitial genes between TMPRSS2 and ERG during the fusion event and 21 had retained these genes. Eighteen of the 21 prostate cancers that had retained the interstitial genes during TMPRSS2-ERG gene fusion were in the very-low risk and low-risk groups.

Information on whether a patient went on to have a biochemical recurrence was available for 34 patients who had prostate cancer with a TMPRSS2-ERG gene fusion with interstitial gene deletion and 22 patients who had prostate cancer with a TMPRSS2-ERG gene fusion with interstitial gene retention.

In univariate, but not multivariate, analysis, biochemical recurrence was significantly lower if the prostate cancer had a TMPRSS2-ERG gene fusion with interstitial gene retention compared with those that had interstitial gene deletion.

“Our data support results from other studies in that the presence or absence of a TMPRSS2-ERG gene fusion was not predictive of outcome,” said Dr. Cheville. “But how the gene fusion formed was important; the retention of interstitial genes during the fusion event was more common in very-low risk and low-risk cancers, and there may be genes in this region that suppress or limit tumour growth. There is potential utility for determining the status of interstitial genes in stratifying men with prostate cancer into more well-defined risk groups, but this will require further study before it can be incorporated into clinical practice.”

“The loss or retention of interstitial genes was tied closely to Gleason score, and we did not have enough cases to determine whether or not the type of fusion was an independent marker for biochemical recurrence,” he added. “We need to look at many more samples and also look at patients with higher Gleason scores to determine the extent to which loss of interstitial genes is associated with disease progression.”

The main limitation of the study is the relatively small number of patients analysed in each group.

Reference: http://dx.doi.org/10.1158/0008-5472.CAN-17-0529

SOURCE: American Association for Cancer Research

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