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Prevalence and Prognostic Relevance of Homologous Recombination Repair Gene Mutations in Uterine Serous Carcinoma

Uterine serous carcinoma (USC) is a rare but aggressive subtype of endometrial cancer lacking efficacious treatments. USC bears molecular and pathological resemblance to high-grade serous ovarian cancer, for which mutations in homologous recombination repair (HRR) genes have been associated with bet...

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Autores principales: Dong, Lin, Wang, Tingting, Li, Ning, Yao, Hongwen, Ying, Jianming, Wu, Lingying, Yuan, Guangwen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688566/
https://www.ncbi.nlm.nih.gov/pubmed/36428992
http://dx.doi.org/10.3390/cells11223563
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author Dong, Lin
Wang, Tingting
Li, Ning
Yao, Hongwen
Ying, Jianming
Wu, Lingying
Yuan, Guangwen
author_facet Dong, Lin
Wang, Tingting
Li, Ning
Yao, Hongwen
Ying, Jianming
Wu, Lingying
Yuan, Guangwen
author_sort Dong, Lin
collection PubMed
description Uterine serous carcinoma (USC) is a rare but aggressive subtype of endometrial cancer lacking efficacious treatments. USC bears molecular and pathological resemblance to high-grade serous ovarian cancer, for which mutations in homologous recombination repair (HRR) genes have been associated with better treatment outcomes with platinum-based chemotherapy and poly-ADP ribose polymerase 1/2 inhibitors (PARPi). We aimed to investigate the prevalence of tumor HRR (tHRR) gene mutations and its potential prognostic value in USC patients. Sixty consecutive USC patients with available tumor tissue samples and complete follow-up records were included. Tumor mutations in relevant HRR genes were identified using next-generation sequencing and correlated with the progress-free survival (PFS) and disease-specific survival (DSS) of the patients. Among the 60 patients’ USC, 22 (36.7%) carried tumor HRR gene mutations (tHRRmt), with ATM, BRCA1, and BRCA2 being the most frequently mutated genes. Survival analysis showed similar PFS (HR, 0.500; 95% CI, 0.203–1.232; p = 0.132), but significantly longer DSS in the tHRRmt patients than in the HRR gene wild-type (tHRRwt) patients (HR, 0.176; 95% CI, 0.050–0.626; p = 0.007). In FIGO stage III and IV patients, the tHRRmt group also displayed longer DSS than the tHRRwt group (p = 0.008). Notably, USC patients with abnormal p53 in our cohort, both PFS and DSS were significantly longer in the tHRRmt group over the tHRRwt group (p = 0.040 and p = 0.008, respectively). The HRR gene mutations are highly prevalent in USC and may be related to better clinical outcomes as a prognostic marker. Further study is needed to confirm whether tHRRmt patients may benefit from treatments targeting homologous recombination such as platinum and PARPi.
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spelling pubmed-96885662022-11-25 Prevalence and Prognostic Relevance of Homologous Recombination Repair Gene Mutations in Uterine Serous Carcinoma Dong, Lin Wang, Tingting Li, Ning Yao, Hongwen Ying, Jianming Wu, Lingying Yuan, Guangwen Cells Article Uterine serous carcinoma (USC) is a rare but aggressive subtype of endometrial cancer lacking efficacious treatments. USC bears molecular and pathological resemblance to high-grade serous ovarian cancer, for which mutations in homologous recombination repair (HRR) genes have been associated with better treatment outcomes with platinum-based chemotherapy and poly-ADP ribose polymerase 1/2 inhibitors (PARPi). We aimed to investigate the prevalence of tumor HRR (tHRR) gene mutations and its potential prognostic value in USC patients. Sixty consecutive USC patients with available tumor tissue samples and complete follow-up records were included. Tumor mutations in relevant HRR genes were identified using next-generation sequencing and correlated with the progress-free survival (PFS) and disease-specific survival (DSS) of the patients. Among the 60 patients’ USC, 22 (36.7%) carried tumor HRR gene mutations (tHRRmt), with ATM, BRCA1, and BRCA2 being the most frequently mutated genes. Survival analysis showed similar PFS (HR, 0.500; 95% CI, 0.203–1.232; p = 0.132), but significantly longer DSS in the tHRRmt patients than in the HRR gene wild-type (tHRRwt) patients (HR, 0.176; 95% CI, 0.050–0.626; p = 0.007). In FIGO stage III and IV patients, the tHRRmt group also displayed longer DSS than the tHRRwt group (p = 0.008). Notably, USC patients with abnormal p53 in our cohort, both PFS and DSS were significantly longer in the tHRRmt group over the tHRRwt group (p = 0.040 and p = 0.008, respectively). The HRR gene mutations are highly prevalent in USC and may be related to better clinical outcomes as a prognostic marker. Further study is needed to confirm whether tHRRmt patients may benefit from treatments targeting homologous recombination such as platinum and PARPi. MDPI 2022-11-11 /pmc/articles/PMC9688566/ /pubmed/36428992 http://dx.doi.org/10.3390/cells11223563 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dong, Lin
Wang, Tingting
Li, Ning
Yao, Hongwen
Ying, Jianming
Wu, Lingying
Yuan, Guangwen
Prevalence and Prognostic Relevance of Homologous Recombination Repair Gene Mutations in Uterine Serous Carcinoma
title Prevalence and Prognostic Relevance of Homologous Recombination Repair Gene Mutations in Uterine Serous Carcinoma
title_full Prevalence and Prognostic Relevance of Homologous Recombination Repair Gene Mutations in Uterine Serous Carcinoma
title_fullStr Prevalence and Prognostic Relevance of Homologous Recombination Repair Gene Mutations in Uterine Serous Carcinoma
title_full_unstemmed Prevalence and Prognostic Relevance of Homologous Recombination Repair Gene Mutations in Uterine Serous Carcinoma
title_short Prevalence and Prognostic Relevance of Homologous Recombination Repair Gene Mutations in Uterine Serous Carcinoma
title_sort prevalence and prognostic relevance of homologous recombination repair gene mutations in uterine serous carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688566/
https://www.ncbi.nlm.nih.gov/pubmed/36428992
http://dx.doi.org/10.3390/cells11223563
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