PIK3CA mutation is an early event in the development of endometriosis‐associated ovarian clear cell adenocarcinoma
Open accessAbstract
Clear cell adenocarcinoma (CCA), a highly lethal histological subtype of ovarian carcinoma, is a type of human cancer with a high frequency of activating mutations in the PIK3CA gene. In this study, we aimed to determine how these mutations contribute to tumour development of CCAs. Exons 9 and 20 of the PIK3CA gene were analysed by direct genomic DNA sequencing of 23 CCAs with synchronous putative precursor lesions (ie endometriosis adjacent to carcinoma, with or without cytological atypia) and their mutational statuses were compared. Somatic mutations of the PIK3CA gene were detected in 10/23 (43%) carcinomas and in all cases the type of mutation was H1047R in the kinase domain. The identical H1047R mutation was also detected in the coexisting endometriotic epithelium, adjacent to the CCAs, in nine of ten (90%) cases. Moreover, in six of the nine lesions, the H1047R mutation was identified even in the endometrioses lacking cytological atypia. These findings provide evidence that mutations of the PIK3CA gene occur in the putative precursor lesions of CCA, strongly suggesting that they are very early events in tumourigenesis, probably initiating the malignant transformation of endometriosis. A specific kinase inhibitor to mutated PIK3CA may potentially be an effective therapeutic reagent against these carcinomas.
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Detection of PTEN, PIK3CA, and ARID1A mutations in benign or atypical endometriotic lesions, which have also been reported in ovarian clear cell carcinoma and endometrioid carcinoma, supports the possibility of malignant transformation of endometriosis.
“Recently, the detection of PTEN, PIK3CA, and ARID1A mutations in benign or atypical endometriotic lesions [15][16][17], which have been also reported in ovarian clear cell carcinoma and endometrioid carcinoma, supports the possibility of malignant transformation of endometriosis.”
From Malignancies Associated with Extraovarian Endometriosis: A Literature Review (2021) · cites this paper as [17]
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Malignancies Associated with Extraovarian Endometriosis: A Literature Review
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- Authors
- Yamamoto, S., Tsuda, H., Takano, M., Iwaya, K., Tamai, S., & Matsubara, O.
- Affiliations
- National Defense Medical College (JP)
- National Cancer Center Hospital (JP)
- Corresponding author
- Yamamoto, Sohei
- Venue
- The Journal of Pathology
- Publisher
- Wiley
- Published
- 2011-07-07
- Volume
- 225
- Issue
- 2
- Pages
- 189-194
- ISSN
- 0022-3417 (ISSN-L)
- 1096-9896
- OpenAlex
- W2028050295
- Cited by
- 152
- References
- 40
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 7 · 2023: 10 · 2022: 6 · 2021: 8 · 2020: 9 · 2019: 12 · 2018: 13 · 2017: 6 · 2016: 10 · 2015: 16 · 2014: 10 · 2013: 17 · 2012: 11
- FWCI
- 15.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Pathology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Defence, Japan
- Ministry of Health, Labour, and Welfare, Japan
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- PIK3CA mutation, endometriosis, precursor lesions, synchronous lesions, tumourigenesis, malignant transformation, PI3K/Akt signaling, kinase inhibitor therapy
- MeSH terms
- Adult, Endometriosis, Female, Humans, Middle Aged, Mutation, Neoplasm Staging, Ovarian Neoplasms, Precancerous Conditions, Adenocarcinoma, Clear Cell, Phosphatidylinositol 3-Kinases, Reverse Transcriptase Polymerase Chain Reaction, Class I Phosphatidylinositol 3-Kinases
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