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Detection of endometrial cancer via molecular analysis of DNA collected with vaginal tampons.
Open accessAbstract
Objective We demonstrate the feasibility of detecting EC by combining minimally-invasive specimen collection techniques with sensitive molecular testing.Methods Prior to hysterectomy for EC or benign indications, women collected vaginal pool samples with intravaginal tampons and underwent endometrial brushing. Specimens underwent pyrosequencing for DNA methylation of genes reported to be hypermethylated in gynecologic cancers and recently identified markers discovered by profiling over 200 ECs. Methylation was evaluated individually across CpGs and averaged across genes. Differences between EC and benign endometrium (BE) were assessed using two-sample t-tests and area under the curve (AUC).Results Thirty-eight ECs and 28 BEs were included. We evaluated 97 CpGs within 12 genes, including previously reported markers (RASSF1, HSP2A, HOXA9, CDH13, HAAO, and GTF2A1) and those identified in discovery work (ASCL2, HTR1B, NPY, HS3ST2, MME, ADCYAP1, and additional CDH13 CpG sites). Mean methylation was higher in tampon specimens from EC v. BE for 9 of 12 genes (ADCYAP1, ASCL2, CDH13, HS3ST2, HTR1B, MME, HAAO, HOXA9, and RASSF1) (all p<0.05). Among these genes, relative hypermethylation was observed in EC v. BE across CpGs. Endometrial brush and tampon results were similar. Within tampon specimens, AUC was highest for HTR1B (0.82), RASSF1 (0.75), and HOXA9 (0.74). This is the first report of HOXA9 hypermethylation in EC.Conclusion DNA hypermethylation in EC tissues can also be identified in vaginal pool DNA collected via intravaginal tampon. Identification of additional EC biomarkers and refined collection methods are needed to develop an early detection tool for EC.
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“Interest has increased in the use of biomarkers, such as DNA methylation, to i mprove early detection of endometrial cancer. 31,32,170,171”
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Metadata
- Authors
- Bakkum-Gamez, J. N., Wentzensen, N., Maurer, M. J., Hawthorne, K. M., Voss, J. S., Kroneman, T. N., Famuyide, A. O., Clayton, A. C., Halling, K. C., Kerr, S. E., Cliby, W. A., Dowdy, S. C., Kipp, B. R., Mariani, A., Oberg, A. L., Podratz, K. C., Shridhar, V., & Sherman, M. E.
- Affiliations
- Mayo Clinic (US)
- National Cancer Institute (US)
- Corresponding author
- Bakkum-Gamez, Jamie N.
- ORCID
- Venue
- Gynecologic Oncology
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 137
- Issue
- 1
- Pages
- 14-22
- ISSN
- 0090-8258 (ISSN-L)
- PMC
- PMC4380654
- OpenAlex
- W2147798100
- Cited by
- 107
- References
- 57
- Citations by year
- 2026: 12 · 2025: 8 · 2024: 11 · 2023: 11 · 2022: 9 · 2021: 15 · 2020: 11 · 2019: 12 · 2018: 6 · 2017: 3 · 2016: 6 · 2015: 3
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gynecologic Oncology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NCI Cancer Center Support (P30 CA 15083)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Keywords
- endometrial cancer, DNA methylation, hypermethylation, vaginal tampons, tumor markers, early cancer detection, HOXA9, RASSF1, 5-HT1B receptor, CpG sites
- MeSH terms
- Aged, DNA, Neoplasm, Female, Humans, Middle Aged, Neoplasm Staging, Pilot Projects, Biomarkers, Tumor, Vagina, Case-Control Studies, Endometrial Neoplasms, CpG Islands, DNA Methylation, Menstrual Hygiene Products
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