Oncogenic gene fusions in nonneoplastic precursors as evidence that bacterial infection can initiate prostate cancer

• DOI: 10.1073/pnas.2018976118
• Publication Date: 2021-08-02T20:36:55Z
• Authors: Eva Shrestha; Jonathan B. Coulter; William Guzman; Busra Ozbek; Megan M. Hess; Luke Mummert; Sarah E. Ernst; Janielle P. Maynard; Alan K. Meeker; Christopher M. He...; Michael C. Haffner; Angelo M. De Marzo; Karen S. Sfanos
• Keywords: Male; Prostatectomy; 0301 basic medicine; DNA Breaks; Serine Endopeptidases; Prostate; Prostatic Neoplasms; Bacterial Infections; Prostatitis; 3. Good health; 03 medical and health sciences; Transcriptional Regulator ERG; Polyketides; Humans; Oncogene Fusion; Atrophy; Peptides

Significance Prostate infections and inflammation are potential initiating factors in prostate cancer development. Here, we investigated whether bacterial infections are associated with the presence of the most common prostate cancer oncogenic gene fusion, TMPRSS2:ERG, in early precursor lesions. We provide evidence that TMPRSS2:ERG (ERG+) gene fusions can initiate in early prostate cancer risk factor lesions, including proliferative inflammatory atrophy in the setting of prostate infection. We further demonstrate that these infection-associated ERG+ precursor lesions are transitioning to early invasive cancer. Overall, we provide evidence that, in at least a subset of cases, infection-induced TMPRSS2:ERG gene fusions are an early alteration in the carcinogenic process.