The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
PIK3CA and PTEN Mutations in Uterine Endometrioid Carcinoma and Complex Atypical Hyperplasia
Abstract
Purpose: The tumor suppressor PTEN gene and the PIK3CA oncogene are frequently mutated in uterine endometrioid carcinoma (UEC). PTEN mutations are also common in complex atypical hyperplasia (CAH), the precursor lesion of UEC. The status of PIK3CA has not yet been explored in CAH. In this study, we evaluated both CAH and UEC for PTEN and PIK3CA mutations. Experimental Design: Neoplastic tissue was microdissected, and DNA was extracted from 29 cases of CAH. DNA was available from 44 UEC cases previously characterized for PTEN mutations. Direct DNA sequencing of exons 9 and 20 of the PIK3CA gene was done on all 73 cases. In addition, CAH cases were analyzed for PTEN mutations. Statistical analyses were done using the Fisher's exact test. Results: Two (7%) of 29 CAH and 17 (39%) of 44 UEC cases contained a PIK3CA mutation (P = 0.003). Fourteen (48%) of 29 CAH cases had a PTEN mutation, but none contained both a PTEN and PIK3CA mutation. Twenty-five (57%) of 44 UEC cases had a PTEN mutation, and 12 (48%) of these 25 cases also contained a PIK3CA mutation. Coexistent PIK3CA and PTEN mutations were significantly correlated with UEC compared with CAH (P = 0.002), but the association in UEC did not reach statistical significance (P = 0.21). Conclusions: PIK3CA is the most commonly mutated oncogene in UEC; however, mutations are uncommon in CAH. Thus, mutations in PIK3CA, unlike PTEN mutations, are associated with invasion. These findings suggest that mutations in PIK3CA may serve as a marker of invasion with potential clinical use. Furthermore, PIK3CA and PTEN mutations may play distinct roles in endometrial tumorigenesis.
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“While this hypothesis has been previously proposed48,50–52, it had never before been tested in an isogenic model.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [50]
In the citing paper
“thereby overcoming a major bottleneck to successfully model early endometrial tumorigenesis50.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [50]
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“Taken together, these results demonstrate the significant advantage the toolkit we have developed in this study has to generate isogenic models of novel mutations in early tumorigenesis48,50–52.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [50]
Citations
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Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic
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Self-citationMolecular targets for cancer therapy in the PI3K/AKT/mTOR pathway
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Classification of endometrial carcinoma: more than two types
Murali, R., Soslow, R. A., & Weigelt, B. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70591-6 · Cited by 649
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Metadata
- Authors
- Hayes, M. P., Wang, H., Espinal-Witter, R., Douglas, W., Solomon, G. J., Baker, S. J., & Ellenson, L. H.
- Affiliations
- Cornell University (US)
- St. Jude Children's Research Hospital (US)
- Venue
- Clinical Cancer Research
- Published
- 2006-10-15
- Volume
- 12
- Issue
- 20
- Pages
- 5932-5935
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2101549875
- Cited by
- 218
- References
- 23
- Citations by year
- 2025: 6 · 2024: 10 · 2023: 9 · 2022: 5 · 2021: 4 · 2020: 3 · 2019: 19 · 2018: 16 · 2017: 11 · 2016: 15 · 2015: 12 · 2014: 11 · 2013: 17 · 2012: 21
- FWCI
- 13.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA095427, CA 095427)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Keywords
- PIK3CA mutation, PTEN mutation, endometrioid endometrial cancer, complex atypical hyperplasia, endometrial tumorigenesis, tumor invasion, co-occurring mutations, precursor lesions
- MeSH terms
- DNA, Neoplasm, Endometrium, Female, Humans, Hyperplasia, Mutation, Uterine Neoplasms, Endometrial Neoplasms, Phosphatidylinositol 3-Kinases, PTEN Phosphohydrolase, Class I Phosphatidylinositol 3-Kinases
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