PLK3 amplification and tumor immune microenvironment of metastatic tumors are linked to adjuvant treatment outcomes in uterine serous cancer. Issue 3 (27th September 2022)

• Record Type: Journal Article
• Authors: Jones, Wendell; Tait, David; Livasy, Chad; Ganapathi, Mahrukh; Ganapathi, Ram
• Is Part Of: NAR cancer. Volumer 4:Issue 3(2022)
• Publication Date: 2022-09-27
• Subjects: Cancer -- Periodicals; Cancer -- Genetic aspects -- Periodicals; Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 616.994
• DOI: 10.1093/narcan/zcac026
• Languages: English
• ISSNs: 2632-8674

Abstract

Abstract: Uterine serous carcinoma (USC), an aggressive variant of endometrial cancer representing approximately 10% of endometrial cancer diagnoses, accounts for ∼39% of endometrial cancer-related deaths. We examined the role of genomic alterations in advanced-stage USC associated with outcome using paired primary-metastatic tumors ( n = 29) treated with adjuvant platinum and taxane chemotherapy. Comparative genomic analysis of paired primary-metastatic patient tumors included whole exome sequencing and targeted gene expression. Both PLK3 amplification and the tumor immune microenvironment (TIME) in metastatic tumors were linked to time-to-recurrence (TTR) risk without any such association observed with primary tumors. TP53 loss was significantly more frequent in metastatic tumors of platinum-resistant versus platinum-sensitive patients and was also associated with increased recurrence and mortality risk. Increased levels of chr1 breakpoints in USC metastatic versus primary tumors co-occur with PLK3 amplification. PLK3 and the TIME are potential targets for improving outcomes in USC adjuvant therapy. Graphical Abstract: