Talayeh Ghezelayagh
Instructor, Obstetrics & Gynecology - Gynecologic Oncology
Clinical Focus
- Gynecologic Oncology
Professional Education
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Fellowship: University of Washington Gynecologic Oncology Fellowship (2023) WA
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Board Certification: American Board of Obstetrics and Gynecology, Obstetrics and Gynecology (2022)
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Residency: University of Washington Obstetrics and Gynecology Residency (2019) WA
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Medical Education: University of California at San Francisco School of Medicine (2015) CA
All Publications
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TP53 somatic evolution in cervical liquid-based cytology and blood from individuals with and without ovarian cancer and BRCA1 or BRCA2 germline mutations.
Oncogene
2024
Abstract
Somatic TP53 mutations are prevalent in normal tissue but little is known about their association with cancer risk. Cervical liquid-based cytology (LBC), commonly known as Pap test, provides an accessible gynecological sample to test the value of TP53 somatic mutations as a biomarker for high-grade serous ovarian cancer (HGSC), a cancer type mostly driven by TP53 mutations. We used ultra-deep duplex sequencing to analyze TP53 mutations in LBC and blood samples from 70 individuals (30 with and 40 without HGSC) undergoing gynecologic surgery, 30 carrying BRCA1 or BRCA2 germline pathogenic variants (BRCApv). Only 30% of the tumor mutations were found in LBC samples. However, TP53 pathogenic mutations were identified in nearly all LBC and blood samples, with only 5.4% of mutations in LBC (20/368) also found in the corresponding blood sample. TP53 mutations were more abundant in LBC than in blood and increased with age in both sample types. BRCApv carriers with HGSC had more TP53 clonal expansions in LBC than BRCApv carriers without cancer. Our results show that, while not useful for direct cancer detection, LBC samples capture TP53 mutation burden in the gynecological tract, presenting potential value for cancer risk assessment in individuals at higher hereditary risk for ovarian cancer.
View details for DOI 10.1038/s41388-024-03089-y
View details for PubMedID 38918516
View details for PubMedCentralID 9763223