BRIEF RESEARCH REPORT article
Front. Oncol.
Sec. Gynecological Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1573801
This article is part of the Research TopicExploring Molecular Mechanisms in Cancer through Tumor Molecular PathologyView all 6 articles
TP53 and KRAS co-mutations are associated with worse outcomes in mucinous ovarian carcinomas
Provisionally accepted
Yingao Zhang1
Savannah Barkdull1
Panayiotis Kontoyiannis2
Alejandra Flores Legarreta3David M Gershenson3Preetha Ramalingam4
Michael Frumovitz3
Anil Sood3*- 1Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, United States
- 2McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, United States
- 3Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
- 4Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States
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Mucinous 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.All 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. Forty patients were included in this retrospective cohort; 34 (85%) had at least 1 genomic alteration on TMP (median 3, 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 (aHR 4.02, 95% 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). A 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.
Keywords: Mucinous adenocarcinoma, ovarian cancer, TP53, KRAS, Molecular sequencing, NGS, Genomic sequencing, tumor mutation
Received: 09 Feb 2025; Accepted: 07 Jul 2025.
Copyright: © 2025 Zhang, Barkdull, Kontoyiannis, Flores Legarreta, Gershenson, Ramalingam, Frumovitz and Sood. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Anil Sood, Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, 77230, Texas, United States
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