Cited by 600Ovarian cancer diagnosis and treatmentBRCA gene mutations in cancerPARP inhibition in cancer therapy

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Transformation of the Fallopian Tube Secretory Epithelium Leads to High-Grade Serous Ovarian Cancer in Brca;Tp53;Pten Models

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Perets, Ruth, Wyant, Gregory A., Muto, Katherine W., Bijron, Jonathan G., Poole, Barish B., Chin, Kenneth T., Chen, Jin Yun H., Ohman, Anders W., Stepule, Corey D., Kwak, Soongu, Karst, Alison M., Hirsch, Michelle S., Setlur, Sunita R., Crum, Christopher P., Dinulescu, Daniela M., Drapkin, Ronny·2013·Cancer Cell

DOI 10.1016/j.ccr.2013.10.013PMC PMC3917315

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Abstract

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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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: Perets, Ruth
Wyant, Gregory A.
Hirsch, Michelle S.
Setlur, Sunita R.
Crum, Christopher P.
Dinulescu, Daniela M.
Drapkin, Ronny
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2013-12
Volume: 24
Issue: 6
Pages: 751-765
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccr.2013.10.013
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 373 d)
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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Transformation of the Fallopian Tube Secretory Epithelium Leads to High-Grade Serous Ovarian Cancer in Brca;Tp53;Pten Models

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