Study Identifies Distinct, Potentially Targetable Mutations in Metastatic Versus Primary Prostate Cancer

Metastatic prostate cancer features distinct genetic aberrations from primary prostate cancer, suggesting potential new future opportunities for more targeted therapy in aggressive disease, according to a study presented at the 2022 American Urological Association Annual Meeting.

According to Seung-Hwan Jeong, MD, from the Seoul National University Hospital, Seoul, South Korea, who presented the research findings, information obtained from next-generation sequencing in recent years has significantly improved oncogenomics “to defining cancer-related genes including oncogenes and tumor suppressor genes facilitating detailed diagnosis, enhanced anticipation of the prognosis, and precision medicine for each patient” with cancer.

For their study, Dr. Jeong and colleagues collected targeted sequencing data from 93 patients with prostate cancer. The investigators identified tissue origins of each case and classified cases into either prostate or metastatic sites. In each group, the researchers analyzed the pooled data using OncoPrint through cBioportal. Finally, the researchers comparatively analyzed genetic aberrations to identify significant genes that represented each group.

Out of the 93 patients who underwent targeted-sequencing using FIRST-cancer panel version 3.2, a total of 13 cases were from a distant metastasis site, while 80 cases of next-generation sequencing were performed on the samples from the prostate (primary group).

The investigators drew OncoPrint through cBioPortal to visualize the different genetic aberrations. Genes were presented in a descending order of the mutation frequencies in both groups.

For instance, the top 5 genes most frequently altered in the primary group included FOXA1, RB1, BRCA2, TP53, and SPOP. In the cases from a distant metastasis site, the top 5 most frequently altered genes were FANCA, TMPRSS, ERG, TP53, and PTEN. Both groups therefore shared the TP53 gene alteration.

The proportional analysis of each group found that the contributing genes for metastasis included UGT1A1, NRG1, and FANCA. According to a survival analysis conducted on The Cancer Genome Atlas program data, patients with mutated UGT1A1 or NRG1 had a poor overall survival.