气候变化领域集成服务门户(CCPortal): Oncogenic gene fusions in nonneoplastic precursors as evidence that bacterial infection can initiate prostate cancer

CCPortal

DOI	10.1073/pnas.2018976118
	Oncogenic gene fusions in nonneoplastic precursors as evidence that bacterial infection can initiate prostate cancer
	Shrestha E.; Coulter J.B.; Guzman W.; Ozbek B.; Hess M.M.; Mummert L.; Ernst S.E.; Maynard J.P.; Meeker A.K.; Heaphy C.M.; Haffner M.C.; de Marzo A.M.; Sfanos K.S.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:32
英文摘要	Prostate adenocarcinoma is the second most commonly diagnosed cancer in men worldwide, and the initiating factors are unknown. Oncogenic TMPRSS2:ERG (ERG+) gene fusions are facilitated by DNA breaks and occur in up to 50% of prostate cancers. Infection-driven inflammation is implicated in the formation of ERG+ fusions, and we hypothesized that these fusions initiate in early inflammation-associated prostate cancer precursor lesions, such as proliferative inflammatory atrophy (PIA), prior to cancer development. We investigated whether bacterial prostatitis is associated with ERG+ precancerous lesions in unique cases with active bacterial infections at the time of radical prostatectomy. We identified a high frequency of ERG+ non–neoplastic-appearing glands in these cases, including ERG+ PIA transitioning to early invasive cancer. These lesions were positive for ERG protein by immunohistochemistry and ERG messenger RNA by in situ hybridization. We additionally verified TMPRSS2:ERG genomic rearrangements in precursor lesions using tricolor fluorescence in situ hybridization. Identification of rearrangement patterns combined with whole-prostate mapping in three dimensions confirmed multiple (up to eight) distinct ERG+ precancerous lesions in infected cases. We further identified the pathogen-derived genotoxin colibactin as a potential source of DNA breaks in clinical cases as well as cultured prostate cells. Overall, we provide evidence that bacterial infections can initiate driver gene alterations in prostate cancer. In addition, our observations indicate that infection-induced ERG+ fusions are an early alteration in the carcinogenic process and that PIA may serve as a direct precursor to prostate cancer. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Colibactin; Infection; Inflammation; Prostate cancer; TMPRSS2:ERG fusion
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238837
作者单位	Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States; Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States; Department of Art as Applied to Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
推荐引用方式 GB/T 7714	Shrestha E.,Coulter J.B.,Guzman W.,et al. Oncogenic gene fusions in nonneoplastic precursors as evidence that bacterial infection can initiate prostate cancer[J],2021,118(32).
APA	Shrestha E..,Coulter J.B..,Guzman W..,Ozbek B..,Hess M.M..,...&Sfanos K.S..(2021).Oncogenic gene fusions in nonneoplastic precursors as evidence that bacterial infection can initiate prostate cancer.Proceedings of the National Academy of Sciences of the United States of America,118(32).
MLA	Shrestha E.,et al."Oncogenic gene fusions in nonneoplastic precursors as evidence that bacterial infection can initiate prostate cancer".Proceedings of the National Academy of Sciences of the United States of America 118.32(2021).