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Transformation of the Fallopian Tube Secretory Epithelium Leads to High-Grade Serous Ovarian Cancer in Brca;Tp53;Pten Models
Open accessAbstract
High-grade serous ovarian carcinoma presents significant clinical and therapeutic challenges. Although the traditional model of carcinogenesis has focused on the ovary as a tumor initiation site, recent studies suggest that there may be additional sites of origin outside the ovary, namely the secretory cells of the fallopian tube. Our study demonstrates that high-grade serous tumors can originate in fallopian tubal secretory epithelial cells and also establishes serous tubal intraepithelial carcinoma as the precursor lesion to high-grade serous ovarian and peritoneal carcinomas in animal models targeting the Brca, Tp53, and Pten genes. These findings offer an avenue to address clinically important questions that are critical for cancer prevention and early detection in women carrying BRCA1 and BRCA2 mutations.
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“Conditional knockout mice, using the Cre-lox system for cell type specificity, have been used to reproduce oncogenic mutations and HR defects to study ovarian cancer development and responses to clinically relevant treatments such as platin-based drugs and PARPis (Szabova et al., 2012; Perets et al., 2013; Szabova et al., 2014; Zhai et al., 2017).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Perets et al., 2013
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Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer
Bowtell, D. D. L., Böhm, S., Ahmed, A. A., Aspuria, P.-J. P., Bast, R. C., Beral, V., Berek, J. S., Birrer, M. J., Blagden, S. P., Bookman, M. A., et al. (2015) · Nature reviews. Cancer · doi:10.1038/nrc4019 · Cited by 1,395
Matulonis, U. A., Sood, A. K., Fallowfield, L., Howitt, B. E., Sehouli, J., & Karlan, B. Y. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.61 · Cited by 1,362
Chehelgerdi, M., Chehelgerdi, M., Allela, O. Q. B., Pecho, R. D. C., Narayanan, J., Rao, D. P., Thamaraikani, T., Vasanthan, M., Viktor, P., Lakshmaiya, N., et al. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01865-0 · Cited by 1,132
The Dualistic Model of Ovarian Carcinogenesis
Kurman, R. J., & Shih, I. (2016) · American Journal Of Pathology · doi:10.1016/j.ajpath.2015.11.011 · Cited by 972
High grade serous ovarian carcinomas originate in the fallopian tube
Labidi‐Galy, S. I., Papp, E., Hallberg, D. L., Niknafs, N., Adleff, V., Noë, M., Bhattacharya, R., Novak, M., Jones, S., Phallen, J. A., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00962-1 · Cited by 762
Metadata
- Authors
- Perets, R., Wyant, G. A., Muto, K. W., Bijron, J. G., Poole, B. B., Chin, K. T., Chen, J. Y. H., Ohman, A. W., Stepule, C. D., Kwak, S., Karst, A. M., Hirsch, M. S., Setlur, S. R., Crum, C. P., Dinulescu, D. M., & Drapkin, R.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Dinulescu, Daniela M.
- Drapkin, Ronny
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 24
- Issue
- 6
- Pages
- 751-765
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3917315
- OpenAlex
- W2013107316
- Cited by
- 596
- References
- 58
- Citations by year
- 2026: 23 · 2025: 49 · 2024: 35 · 2023: 47 · 2022: 47 · 2021: 46 · 2020: 85 · 2019: 44 · 2018: 42 · 2017: 44 · 2016: 51 · 2015: 49 · 2014: 32
- FWCI
- 52.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust
- National Institutes of Health
- National Cancer Institute (R21CA156021, U01CA152990, P50CA105009)
- Topics
- Health Sciences › Medicine › Oncology › Ovarian cancer diagnosis and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- high-grade serous ovarian cancer, serous tubal intraepithelial carcinoma, cancer of unknown primary, BRCA1, BRCA2, TP53, PTEN, peritoneal cancer, precursor lesions, cancer prevention, early detection
- MeSH terms
- PAX8 Transcription Factor, Animals, Cell Transformation, Neoplastic, Epithelium, Fallopian Tube Neoplasms, Female, Mice, Inbred C57BL, Ovarian Neoplasms, Precancerous Conditions, Genes, p53, Cystadenocarcinoma, Serous, Genes, BRCA1, Integrases, Genes, BRCA2, PTEN Phosphohydrolase, Mice, Paired Box Transcription Factors, Neoplasm Grading
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