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Cancer-Associated Mutations in Endometriosis without Cancer
Open accessAbstract
BACKGROUND: Endometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% of reproductive-age women and can cause pelvic pain and infertility. Endometriotic lesions are considered to be benign inflammatory lesions but have cancerlike features such as local invasion and resistance to apoptosis. METHODS: We analyzed deeply infiltrating endometriotic lesions from 27 patients by means of exomewide sequencing (24 patients) or cancer-driver targeted sequencing (3 patients). Mutations were validated with the use of digital genomic methods in microdissected epithelium and stroma. Epithelial and stromal components of lesions from an additional 12 patients were analyzed by means of a droplet digital polymerase-chain-reaction (PCR) assay for recurrent activating KRAS mutations. RESULTS: Exome sequencing revealed somatic mutations in 19 of 24 patients (79%). Five patients harbored known cancer driver mutations in ARID1A, PIK3CA, KRAS, or PPP2R1A, which were validated by Safe-Sequencing System or immunohistochemical analysis. The likelihood of driver genes being affected at this rate in the absence of selection was estimated at P=0.001 (binomial test). Targeted sequencing and a droplet digital PCR assay identified KRAS mutations in 2 of 3 patients and 3 of 12 patients, respectively, with mutations in the epithelium but not the stroma. One patient harbored two different KRAS mutations, c.35G→T and c.35G→C, and another carried identical KRAS c.35G→A mutations in three distinct lesions. CONCLUSIONS: We found that lesions in deep infiltrating endometriosis, which are associated with virtually no risk of malignant transformation, harbor somatic cancer driver mutations. Ten of 39 deep infiltrating lesions (26%) carried driver mutations; all the tested somatic mutations appeared to be confined to the epithelial compartment of endometriotic lesions.
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In the citing paper
“While nucleotide variants or mutations were noted sporadically in the epithelial component of ovarian endometriomas or deep-infiltrating endometriosis, stromal cells consistently lack any somatic mutations (Anglesio et al., 2017).”
From Endometriosis and nuclear receptors (2019) · cites this paper as Anglesio et al., 2017
Experimental — accuracy not yet measuredIn the citing paper
“Recently, molecular biology techniques using a next‐generation sequencing have also provided clues to the origin of endometriosis and pathogenesis that cannot be elucidated by epidemiological investigations alone.”
From Extra-pelvic endometriosis: a review. (2020) · cites this paper as [104]
In the citing paper
“Cancer genomic mutations have also been reported for extraovarian endometriosis in recent years, and mutations in cancer-associated genes, such as PIK3CA, KRAS, and ARID1A, have been identified [106].”
From Malignancies Associated with Extraovarian Endometriosis: A Literature Review (2021) · cites this paper as [106]
In the citing paper
“Cancer genomic mutations have also been reported for extraovarian endometriosis in recent years, and mutations in cancer-associated genes, such as PIK3CA, KRAS, and ARID1A, have been identified [106].”
From Malignancies Associated with Extraovarian Endometriosis: A Literature Review (2021) · cites this paper as [106]
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Cites
Stratton, M. R., Campbell, P. J., & Futreal, P. A. (2009) · Nature · doi:10.1038/nature07943 · Cited by 3,625
Sampson, J. A. (1927) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(15)30003-x · Cited by 2,334
COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer
Forbes, S. A., Bindal, N., Bamford, S., Cole, C., Kok, C. Y., Beare, D., Jia, M., Shepherd, R., Leung, K., Menzies, A., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq929 · Cited by 2,278
Giudice, L. C. (2010) · New England Journal of Medicine · doi:10.1056/nejmcp1000274 · Cited by 1,924
Bulun, S. E. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0804690 · Cited by 1,772
High burden and pervasive positive selection of somatic mutations in normal human skin
Martincorena, I., Roshan, A., Gerstung, M., Ellis, P., Van Loo, P., McLaren, S., Wedge, D. C., Fullam, A., Alexandrov, L. B., Tubio, J. M., et al. (2015) · Science · doi:10.1126/science.aaa6806 · Cited by 1,770
ARID1A Mutations in Endometriosis-Associated Ovarian Carcinomas
Wiegand, K. C., Shah, S. P., Al-Agha, O. M., Zhao, Y., Tse, K., Zeng, T., Senz, J., McConechy, M. K., Anglesio, M. S., Kalloger, S. E., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1008433 · Cited by 1,712
Self-citationDetection and quantification of rare mutations with massively parallel sequencing
Kinde, I., Wu, J., Papadopoulos, N., Kinzler, K. W., & Vogelstein, B. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1105422108 · Cited by 1,144
Self-citationSimoens, S., Dunselman, G., Dirksen, C., Hummelshoj, L., Bokor, A., Brandes, I., Brodszky, V., Canis, M., Colombo, G. L., DeLeire, T., et al. (2012) · Human Reproduction · doi:10.1093/humrep/des073 · Cited by 1,070
(1927) · PubMed Central · Cited by 1,008
Flagged first, then by citations
Research works printed but not linked: 4
- Ferguson BR, 1969, Obstet Gynecol, 33, 617
- Sampson JA, 1927, Am J Pathol, 3, 93
- Sato N, 2000, Cancer Res, 60, 7052
- Cullen TS. Adenoma-myoma uteri diffusum benignum. Johns Hopkins Hosp Bull 1896;6:133-7.
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Items 601–629 of 629
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Chilà, C., Kermarrec, É., Loi, V., Ilic, J., Zerbib, E., Ferrier, C., Dahan, M., Dabi, Y., Touboul, C., & Daraï, É. (2026) · Journal of Gynecology Obstetrics and Human Reproduction · doi:10.1016/j.jogoh.2026.103200
Research Progress on Endometriosis-Associated Ovarian Cancer
余, 平. (2026) · Advances in Clinical Medicine · doi:10.12677/acm.2026.1651847
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Subramaniam, S., Gargett, C. E., Fitzgerald, H. C., Montgomery, G. W., & McKinnon, B. D. (2026) · Molecular Human Reproduction · doi:10.1093/molehr/gaag027 · Cited by 1
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Wang, W., Chen, Y. C., Wang, W., Jiang, L., Bai, D., Yang, Y. F., Wang, H., Wang, M., Si, H., Long, J., et al. (2026) · Molecular Immunology · doi:10.1016/j.molimm.2026.05.008
Jamshed, A., Zhu, F., Cartwright, D., Turner, K., Amin, K., Khalifa, M. A., Adeyi, O. A., Mukhtar, Z., & Park, B. U. (2026) · Human Pathology · doi:10.1016/j.humpath.2026.106171
Kuroda, T., Giannone, G., Ennis, D. P., Mirza, H., Marks, D., Flood, L., Sisley, M., Griffin, R., Desai, S., McDermott, J. R., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.29.728698
Dubovecak, M., Turudić, T. P., Luetić, A. T., Hafner, D., Klenkar, M., Cvrtila, S., & Medić, N. (2026) · Middle East Fertility Society Journal · doi:10.1186/s43043-026-00346-w
Shibata, T., Takata, E., Shioya, A., Yamada, S., Ura, H., Niida, Y., Yasumoto, K., & Takakura, M. (2026) · JCO Precision Oncology · doi:10.1200/po-26-00056
Gu, Y., Zhao, X., Shi, Y., Hu, Z., Liu, Q. F., Zhu, H., Li, P., & Liu, K. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1709462
Coté, J. J., Coté, R. D., Kennedy, K., Block, M. S., Farias‐Eisner, R., Walters, R. W., & Conrad, L. B. (2026) · Journal of Minimally Invasive Gynecology · doi:10.1016/j.jmig.2026.06.015
Building Disease Models for Endometriosis: iPSCs as Game-Changers
Kahar, K. H., E-Anjum, B., Nordin, F., Ng, A. M.-H., Aziz, N. H. A., Idris, I. M., Tye, G. J., & Zaman, W. S. W. K. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27125614
Zeng, C., Zhu, J., Lu, R., Wu, P., Li, X., Li, F., Peng, C., 周应芳, & Xue, Q. (2026) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003770 · Cited by 1
Genomic profiling as an option for ovarian cancer diagnostics
Paolis, E. D., Raspaglio, G., Donato, M. D., Tulli, E., Mattei, I., & Minucci, A. (2026) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2026.2700342
Chen, L., Severino, E., Wu, D.-S., Singh, B., Segars, J. H., & Shih, I. (2026) · Biomedicines · doi:10.3390/biomedicines14071636
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Anastasiu, C. V., Dimienescu, O. G., Dinuță-Smeu, M. A., Moga, M., Grigorescu, D. O., Gugiu, G., & Bisoc, A. (2026) · Medicina · doi:10.3390/medicina62081577
Iacobelli, V., Mastrantoni, L., Alivernini, S., Scaglione, G., Agostini, A., Mantini, G., Piermattei, A., Persiani, F., Camarda, F., Trozzi, R., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-10497180/v1
Transcriptome differences in lesions by color, and cancer mutations in endometriosis
Huang, J. Y., Relovská, S., Madnani, R. S., Li, L., Liu, S., Milne, A., Waldman, I. N., Seshan, M. L., Lindholm, A. E., Disler, E. R., et al. (2026) · Reproduction and Fertility · doi:10.1530/raf-26-0057
Self-citationThe role of SYNE1/2 variants as a potential predisposition factor for the onset of endometriosis
Santin, A., Pegoraro, S., Toffoli, M., Pianigiani, G., Balduit, A., Zito, G., Mangogna, A., Trevisiol, P., Rosso, L. E., Mannino, F., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1888334
Genetic architecture of endometriosis: risk factors, comorbidities and clinical implications
Montgomery, G. W., McGrath, I. M., Overgaard, M. T., Nyegaard, M., & Mortlock, S. (2026) · Human Reproduction Update · doi:10.1093/humupd/dmag023
Ammous-Boukhris, N., Abdelmaksoud‐Dammak, R., Feki, A., Khemiri, S., Charfi, S., Sallemi-Boudawara, T., Daoud, J., Khanfir, A., & Mokdad‐Gargouri, R. (2026) · Cancer Reports · doi:10.1002/cnr2.70658
Kwas, K., Lisińska, W., Koziróg, E., Stanek, K., Wolder, D. P., Szubert, M., & Wilczyński, J. R. (2026) · Cancers · doi:10.3390/cancers18183036
Cancer‐associated mutations in endometriosis reframe a benign disease through molecular oncology
Mujacic, C., Vitale, M. C., Siino, R., Giovanni, E. D., Bannera, C. F., Marco, E. D., Gottardo, A., Russo, T. D. B., Barraco, N., Perez, A., et al. (2026) · Molecular Oncology · doi:10.1002/1878-0261.70295
Organoids: Current Applications and Future Directions
Leng, Y., Wang, Y., Cao, C., Deng, F., Lian, W., Chen, X., Lin, M., Zeng, Z., Mo, D., Li, S., et al. (2026) · MedComm · doi:10.1002/mco2.70965
Self-citationMalignant transformation of endometriosis and endometriomas
Cunha, G. V., ROCHA, S. G., Figueiredo-Dias, M., & Roque, R. (2026) · Academia oncology. · doi:10.20935/acadonco8554
Gutowska, K., Urban, A., Wojtyła, C., Ławicki, S., & Laudański, P. (2026) · Cancers · doi:10.3390/cancers18193241
Masha, F. L., Thobakgale, N. M., & Khaba, M. C. (2026) · Journal of the Colleges of Medicine of South Africa · doi:10.4102/jcmsa.v4i1.421
Liu, S., & Sun, C. (2026) · Cancer and Metastasis Reviews · doi:10.1007/s10555-026-10385-4
Liu, Z., Liu, Y., Qiang, R., Zhu, Y., Chen, Y., He, Q., Fang, J., Zhou, X., & Wang, Y. (2026) · Biomedicines · doi:10.3390/biomedicines14112436
Self-citation
Metadata
- Authors
- Anglesio, M. S., Papadopoulos, N., Ayhan, A., Nazeran, T. M., Noë, M., Horlings, H. M., Lum, A., Jones, S., Senz, J., Seckin, T., Ho, J., Wu, R.-C., Lac, V., Ogawa, H., Tessier-Cloutier, B., Alhassan, R., Wang, A., Wang, Y., Cohen, J. D., Wong, F., Hasanovic, A., Orr, N., Zhang, M., Popoli, M., McMahon, W., Wood, L. D., Mattox, A., Allaire, C., Segars, J., Williams, C., Tomasetti, C., Boyd, N., Kinzler, K. W., Gilks, C. B., Diaz, L., Wang, T.-L., Vogelstein, B., Yong, P. J., Huntsman, D. G., & Shih, I.-M.
- Affiliations
- University of British Columbia (CA)
- Hiroshima University (JP)
- BC Cancer Agency (CA)
- Howard Hughes Medical Institute (US)
- ORCID
- Anglesio, Michael S.
- Papadopoulos, Nickolas
- Ayhan, Ayse
- Noë, Michaël
- Horlings, Hugo M.
- Lum, Amy
- Jones, Siân
- Senz, Janine
- Seckin, Tamer
- Wu, Ren-Chin
- Lac, Vivian
- Ogawa, Hiroshi
- Wang, Yuxuan
- Cohen, Joshua D.
- Orr, Natasha
- Zhang, Ming
- Popoli, Maria
- Wood, Laura D.
- Mattox, Austin
- Allaire, Catherine
- Segars, James
- Tomasetti, Cristian
- Boyd, Niki
- Kinzler, Kenneth W.
- Gilks, C. Blake
- Diaz, Luis
- Wang, Tian-Li
- Vogelstein, Bert
- Yong, Paul J.
- Shih, Ie-Ming
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2017-05-11
- Volume
- 376
- Issue
- 19
- Pages
- 1835-1848
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC5555376
- OpenAlex
- W2612851374
- Cited by
- 628
- References
- 50
- Citations by year
- 2026: 57 · 2025: 62 · 2024: 51 · 2023: 75 · 2022: 72 · 2021: 75 · 2020: 80 · 2019: 68 · 2018: 69 · 2017: 19
- FWCI
- 74.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA215483, U01CA200469, R01CA057345, T32CA009243, P50CA062924, R37CA057345, P30CA006973)
- National Institute of General Medical Sciences (T32GM007309, T32GM007184)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- endometriosis, deep infiltrating endometriosis, somatic mutations, cancer driver mutations, KRAS mutation, ARID1A, PIK3CA, PPP2R1A, malignant transformation risk, droplet digital PCR
- MeSH terms
- Adult, Cell Transformation, Neoplastic, DNA Mutational Analysis, DNA-Binding Proteins, Endometriosis, Endometrium, Female, Humans, Middle Aged, Mutation, Nuclear Proteins, Transcription Factors, Polymerase Chain Reaction, Proto-Oncogene Proteins p21(ras), Phosphatidylinositol 3-Kinases, Protein Phosphatase 2, Class I Phosphatidylinositol 3-Kinases, Exome
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