ArticleGynecologic oncology2015
TP53 hot spot mutations in ovarian cancer: selective resistance to microtubule stabilizers in vitro and differential survival outcomes from The Cancer Genome Atlas.
Article in Gynecologic oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- A retrospective analysis of taxane-based chemotherapy in small bowel adenocarcinoma.The oncologist · 2026Article
- Leveraging chromatin packing domains to target chemoevasion in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular characterization of ovarian squamous cell carcinoma originating from mature teratoma.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Acquisition of taxane resistance by p53 inactivation in ovarian cancer cells.Acta pharmacologica Sinica · 2022Article
- DNA repair pathways and their roles in drug resistance for lung adenocarcinoma.Molecular biology reports · 2021Review
- Clinical relevance of TP53 hotspot mutations in high-grade serous ovarian cancers.British journal of cancer · 2020Article
- Influence of p53 Isoform Expression on Survival in High-Grade Serous Ovarian Cancers.Scientific reports · 2019Article
- Frequency of Somatic TP53 Mutations in Combination with Known Pathogenic Mutations in Colon Adenocarcinoma, Non-Small Cell Lung Carcinoma, and Gliomas as Identified by Next-Generation Sequencing.Neoplasia (New York, N.Y.) · 2018Article
- Molecularly targeted therapies in cancer: a guide for the nuclear medicine physician.European journal of nuclear medicine and molecular imaging · 2017Review
- Next-Generation Sequencing-based genomic profiling of brain metastases of primary ovarian cancer identifies high number of BRCA-mutations.Journal of neuro-oncology · 2017Observational
- Antiangiogenesis and gene aberration-related therapy may improve overall survival in patients with concurrent KRAS and TP53 hotspot mutant cancer.Oncotarget · 2017Article
- TP53 mutations in epithelial ovarian cancer.Translational cancer research · 2016Article
- Cadherin-6 type 2, K-cadherin (CDH6) is regulated by mutant p53 in the fallopian tube but is not expressed in the ovarian surface.Oncotarget · 2016Article
- Structure-Based Analysis Reveals Cancer Missense Mutations Target Protein Interaction Interfaces.PloS one · 2016Article
- Tumor suppressor genes and their underlying interactions in paclitaxel resistance in cancer therapy.Cancer cell international · 2016Review
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Authors and funding
9 authors at 5 institutions in 1 country.
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Abstract
objectiveTo test if TP53 hot spot mutations (HSMs) confer differential chemotherapy resistance or survival outcomes, the effects of microtubule stabilizers on human ovarian carcinoma cells (OCCs) expressing TP53 HSMs were studied in vitro. Survival outcomes of patients with high grade serous epithelial ovarian carcinoma (HGS EOC) expressing matched HSMs were compared using The Cancer Genome Atlas (TCGA) data.
methodsGrowth inhibition of OCCs transfected with a HSM (m175, m248 or m273) was measured during treatment with paclitaxel, epothilone B (epoB), or ixabepilone. Effects of epoB on p53 expression, phosphorylation, and acetylation, as well as p53-regulated expression of p21 and mdm2 proteins, were determined by Western blot analysis. Expression of p53 target genes P21, GADD45, BAX, PIDD, NF-kB2, PAI-1, and MDR1 was measured by RT-PCR. cBioPortal.org identified patients with codon R175, R248 or R273 HSMs from TCGA data. Survival outcomes were characterized.
resultsp53-m248 confers chemoresistance and is not acetylated during epoB treatment. m273 demonstrated high MDR1 expression and resistance to paclitaxel. P21, GADD45 and PAI-1 expression were down-regulated in mutant OCCs. Optimally cytoreduced patients with codon R273 (n=17), R248 (n=13), R175 (n=7) HSMs, or any other TP53 mutation demonstrated median 14.9, 17.6, 17.8 and 16.9months (p=0.806) progression free survival and 84.1, 33.6, 62.1 and 44.5months (p=0.040) overall survival, respectively.
conclusionsHuman OCCs harboring different TP53 HSMs were selectively resistant to microtubule stabilizers. Patients with different HSMs had significantly different overall survival. Both in vitro data and clinical experience support further studying the outcomes of particular TP53 HSMs.
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