TP53 and KRAS co-mutations are associated with worse outcomes in mucinous ovarian carcinomas
ObjectiveMucinous ovarian carcinomas (mOC) often harbor unique molecular alterations differentiating them from other epithelial ovarian carcinoma subtypes. We sought to characterize the somatic genomic mutation patterns in mOC and elucidate their associations with oncologic outcomes.MethodsAll patie...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1573801/full |
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| author | Yingao Zhang Savannah Barkdull Panayiotis D. Kontoyiannis Alejandra Flores Legarreta David M. Gershenson Preetha Ramalingam Michael M. Frumovitz Anil K. Sood |
| author_facet | Yingao Zhang Savannah Barkdull Panayiotis D. Kontoyiannis Alejandra Flores Legarreta David M. Gershenson Preetha Ramalingam Michael M. Frumovitz Anil K. Sood |
| author_sort | Yingao Zhang |
| collection | DOAJ |
| description | ObjectiveMucinous ovarian carcinomas (mOC) often harbor unique molecular alterations differentiating them from other epithelial ovarian carcinoma subtypes. We sought to characterize the somatic genomic mutation patterns in mOC and elucidate their associations with oncologic outcomes.MethodsAll patients with mOC treated at a single institution between 2005–2023 were identified, and those with validated tumor molecular profiling (TMP) using next-generation sequencing of somatic variants were included. Progression-free survival (PFS) and overall survival (OS) were calculated on a Kaplan-Meier estimator. Multivariable analysis was performed using Cox regression models.ResultsForty patients were included in this retrospective cohort; 34 (85%) had at least 1 genomic alteration on TMP, with a median of 3 mutations (range 0-30). TP53 (68%) and KRAS (63%) were most frequently altered, and 21 patients (53%) had tumors with TP53/KRAS co-mutations. Patients with TP53/KRAS co-mutations were younger (median 27.9 vs 54.1 y, p=0.01) and were more likely to have early-stage disease (86% vs 47%, p=0.02) than patients without these co-mutations. On multivariable analysis, TP53/KRAS co-mutations were associated with decreased PFS (adjusted hazard ratio [aHR] 4.02, 95% confidence interval [CI] 1.46-12.5, p=0.01) and OS (aHR 21.4, 95% CI 4.28-156, p<0.001). On subgroup analysis of stage I tumors (N=27), the presence of TP53/KRAS co-mutations remained independently associated with worse OS (aHR 8.66, 95% CI 1.50-93.8, p=0.03).ConclusionA substantial proportion of mOCs have concurrent TP53 and KRAS alterations on TMP, and this may portend worse survival, even for patients with early-stage disease. TMP could be a useful tool for prognostication and can be considered for patients with mOC at the time of diagnosis. |
| format | Article |
| id | doaj-art-b7ab5ee6646549d9864d5647fa44f294 |
| institution | DOAJ |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj-art-b7ab5ee6646549d9864d5647fa44f2942025-08-20T03:02:51ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-08-011510.3389/fonc.2025.15738011573801TP53 and KRAS co-mutations are associated with worse outcomes in mucinous ovarian carcinomasYingao Zhang0Savannah Barkdull1Panayiotis D. Kontoyiannis2Alejandra Flores Legarreta3David M. Gershenson4Preetha Ramalingam5Michael M. Frumovitz6Anil K. Sood7Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, TX, United StatesDepartment of Obstetrics & Gynecology, Baylor College of Medicine, Houston, TX, United StatesMcGovern Medical School, University of Texas Health Science Center, Houston, TX, United StatesDepartment of Gynecologic Oncology and Reproductive Medicine, University of Texas Medical Doctor (MD) Anderson Cancer Center, Houston, TX, United StatesDepartment of Gynecologic Oncology and Reproductive Medicine, University of Texas Medical Doctor (MD) Anderson Cancer Center, Houston, TX, United StatesDepartment of Anatomical Pathology, University of Texas Medical Doctor (MD) Anderson Cancer Center, Houston, TX, United StatesDepartment of Gynecologic Oncology and Reproductive Medicine, University of Texas Medical Doctor (MD) Anderson Cancer Center, Houston, TX, United StatesDepartment of Gynecologic Oncology and Reproductive Medicine, University of Texas Medical Doctor (MD) Anderson Cancer Center, Houston, TX, United StatesObjectiveMucinous ovarian carcinomas (mOC) often harbor unique molecular alterations differentiating them from other epithelial ovarian carcinoma subtypes. We sought to characterize the somatic genomic mutation patterns in mOC and elucidate their associations with oncologic outcomes.MethodsAll patients with mOC treated at a single institution between 2005–2023 were identified, and those with validated tumor molecular profiling (TMP) using next-generation sequencing of somatic variants were included. Progression-free survival (PFS) and overall survival (OS) were calculated on a Kaplan-Meier estimator. Multivariable analysis was performed using Cox regression models.ResultsForty patients were included in this retrospective cohort; 34 (85%) had at least 1 genomic alteration on TMP, with a median of 3 mutations (range 0-30). TP53 (68%) and KRAS (63%) were most frequently altered, and 21 patients (53%) had tumors with TP53/KRAS co-mutations. Patients with TP53/KRAS co-mutations were younger (median 27.9 vs 54.1 y, p=0.01) and were more likely to have early-stage disease (86% vs 47%, p=0.02) than patients without these co-mutations. On multivariable analysis, TP53/KRAS co-mutations were associated with decreased PFS (adjusted hazard ratio [aHR] 4.02, 95% confidence interval [CI] 1.46-12.5, p=0.01) and OS (aHR 21.4, 95% CI 4.28-156, p<0.001). On subgroup analysis of stage I tumors (N=27), the presence of TP53/KRAS co-mutations remained independently associated with worse OS (aHR 8.66, 95% CI 1.50-93.8, p=0.03).ConclusionA substantial proportion of mOCs have concurrent TP53 and KRAS alterations on TMP, and this may portend worse survival, even for patients with early-stage disease. TMP could be a useful tool for prognostication and can be considered for patients with mOC at the time of diagnosis.https://www.frontiersin.org/articles/10.3389/fonc.2025.1573801/fullmucinous adenocarcinomaovarian cancerTP53molecular sequencingNGSgenomic sequencing |
| spellingShingle | Yingao Zhang Savannah Barkdull Panayiotis D. Kontoyiannis Alejandra Flores Legarreta David M. Gershenson Preetha Ramalingam Michael M. Frumovitz Anil K. Sood TP53 and KRAS co-mutations are associated with worse outcomes in mucinous ovarian carcinomas Frontiers in Oncology mucinous adenocarcinoma ovarian cancer TP53 molecular sequencing NGS genomic sequencing |
| title | TP53 and KRAS co-mutations are associated with worse outcomes in mucinous ovarian carcinomas |
| title_full | TP53 and KRAS co-mutations are associated with worse outcomes in mucinous ovarian carcinomas |
| title_fullStr | TP53 and KRAS co-mutations are associated with worse outcomes in mucinous ovarian carcinomas |
| title_full_unstemmed | TP53 and KRAS co-mutations are associated with worse outcomes in mucinous ovarian carcinomas |
| title_short | TP53 and KRAS co-mutations are associated with worse outcomes in mucinous ovarian carcinomas |
| title_sort | tp53 and kras co mutations are associated with worse outcomes in mucinous ovarian carcinomas |
| topic | mucinous adenocarcinoma ovarian cancer TP53 molecular sequencing NGS genomic sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1573801/full |
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