Survival of patients with structurally-grouped TP53 mutations in ovarian and breast cancers
| Autor: | Shohreh Shahabi, Kunle Odunsi, Brandon Luke L. Seagle, Kevin H. Eng, Monica Dandapani, Judy Y. Yeh |
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| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Oncology medicine.medical_specialty Pathology endocrine system diseases Breast Neoplasms Kaplan-Meier Estimate Biology Cohort Studies 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Breast cancer Internal medicine Outcome Assessment Health Care medicine TP53 gene Humans Missense mutation Progression-free survival Survival analysis Aged Neoplasm Staging Proportional Hazards Models 030304 developmental biology Ovarian Neoplasms 0303 health sciences Binding Sites Proportional hazards model DNA-binding domain Middle Aged medicine.disease Survival Analysis Protein Structure Tertiary 3. Good health chemistry 030220 oncology & carcinogenesis Mutation Female Neoplasm Grading Tumor Suppressor Protein p53 Ovarian cancer biological markers DNA Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.4080 |
| Popis: | The objective of this study was to determine if ovarian cancer patients with a TP53 mutation grouped by location of the mutation within the p53 protein structure exhibit differential survival outcomes. Data from patients with high grade serous ovarian cancer (HGS OvCa) (N = 316) or breast cancer (BrCa) (N = 981) sequenced by The Cancer Genome Atlas (TCGA) was studied by Kaplan-Meier and Cox proportional hazards survival analysis. A TP53 DNA binding domain (BD) missense mutation (MM) occurred in 58.5% (185/316) of HGS OvCas and 16.8% (165/981) of BrCas. Patients with a TP53 DNA BD MM grouped by structural location had significantly different overall survival (OS) and progression free survival (PFS). Median OS (months) of HGS OvCa patients by structural group were: Sheet-loop-helix stabilizers, 31.1; DNA minor groove residue R248, 33.6; Wild-type, 34.2; all other MMs, 44.5; DNA major groove residues, 84.1, and zinc ion coordinating residues, 87.0 (log-rank p = 0.006). PFS of DNA major groove MM cases was longer than TP53 wild-type cases (19.1 versus 10.1 months, log-rank p = 0.038). HGS OvCa and BrCa patients with structurally-grouped TP53 DNA BD MMs have different survival outcomes. |
| Databáze: | OpenAIRE |
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