Retrotransposon methylation profiles and survival in Black women with high-grade serous ovarian carcinoma
Abstract Introduction Retrotransposons (REs) constitute nearly half of the genome and include long terminal repeat (LTR) elements, Long INterspersed Elements (LINE), and Short INterspersed Elements (SINE). REs are typically silenced in somatic tissues via DNA methylation but can be reactivated throu...
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2025-07-01
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| Series: | Clinical Epigenetics |
| Online Access: | https://doi.org/10.1186/s13148-025-01942-9 |
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| author | Christelle Colin-Leitzinger Katherine A. Lawson-Michod Courtney E. Johnson Irma M. Vlasac Sean Yoder Tania Mesa Dana Roeber Chad Huff Michelle A. T. Hildebrandt Kristin Haller Anthony J. Alberg Elisa V. Bandera Melissa Bondy Michele L. Cote Theresa Hastert Edward S. Peters Paul D. Terry Andrew B. Lawson Andrew Berchuck Brooke L. Fridley Jing-Yi Chern Jennifer A. Doherty Jeffrey R. Marks Joellen M. Schildkraut Brock C. Christensen Lucas A. Salas Lauren C. Peres |
| author_facet | Christelle Colin-Leitzinger Katherine A. Lawson-Michod Courtney E. Johnson Irma M. Vlasac Sean Yoder Tania Mesa Dana Roeber Chad Huff Michelle A. T. Hildebrandt Kristin Haller Anthony J. Alberg Elisa V. Bandera Melissa Bondy Michele L. Cote Theresa Hastert Edward S. Peters Paul D. Terry Andrew B. Lawson Andrew Berchuck Brooke L. Fridley Jing-Yi Chern Jennifer A. Doherty Jeffrey R. Marks Joellen M. Schildkraut Brock C. Christensen Lucas A. Salas Lauren C. Peres |
| author_sort | Christelle Colin-Leitzinger |
| collection | DOAJ |
| description | Abstract Introduction Retrotransposons (REs) constitute nearly half of the genome and include long terminal repeat (LTR) elements, Long INterspersed Elements (LINE), and Short INterspersed Elements (SINE). REs are typically silenced in somatic tissues via DNA methylation but can be reactivated through DNA hypomethylation, potentially impacting gene regulation. Here, we investigate genome-scale profiles of RE methylation in high-grade serous ovarian carcinoma (HGSOC) and associations with survival among Black women. Methods Methylation levels of LTR, LINE-1, and Alu (type of SINE) in 200 HGSOC tumors were predicted using a random forest approach and clustered using multiple consensus algorithms. Associations between RE methylation clusters and survival were evaluated using Cox proportional hazard regression, adjusting for age, stage, and debulking status. We performed sensitivity analyses restricted to women with late-stage disease and with adjustment for BRCA1/BRCA2 mutations. Results Two RE methylation clusters were identified. Cluster 1 exhibited a more hypomethylated RE profile (“Active”), while Cluster 2 was more hypermethylated (“Repressed”). No statistically significant differences in patient or clinical characteristics were observed between clusters. Compared to the Active Cluster, the Repressed Cluster was associated with an increased risk of mortality (HR = 2.41; 95% CI 1.04–5.59) and had a lower proportion of T cells. This association was consistent in sensitivity analyses. Conclusion A more hypermethylated RE profile was linked to worse survival among Black women with HGSOC, highlighting the potential of RE methylation as a prognostic biomarker. Further research is needed to understand the underlying biological mechanisms and their implications in ovarian cancer biology and treatment. |
| format | Article |
| id | doaj-art-393df9a892b449a28095b8f043ee9191 |
| institution | Kabale University |
| issn | 1868-7083 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj-art-393df9a892b449a28095b8f043ee91912025-08-20T04:02:54ZengBMCClinical Epigenetics1868-70832025-07-0117111110.1186/s13148-025-01942-9Retrotransposon methylation profiles and survival in Black women with high-grade serous ovarian carcinomaChristelle Colin-Leitzinger0Katherine A. Lawson-Michod1Courtney E. Johnson2Irma M. Vlasac3Sean Yoder4Tania Mesa5Dana Roeber6Chad Huff7Michelle A. T. Hildebrandt8Kristin Haller9Anthony J. Alberg10Elisa V. Bandera11Melissa Bondy12Michele L. Cote13Theresa Hastert14Edward S. Peters15Paul D. Terry16Andrew B. Lawson17Andrew Berchuck18Brooke L. Fridley19Jing-Yi Chern20Jennifer A. Doherty21Jeffrey R. Marks22Joellen M. Schildkraut23Brock C. Christensen24Lucas A. Salas25Lauren C. Peres26Moffitt Cancer CenterPopulation Health Sciences, Huntsman Cancer Institute, University of UtahRollins School of Public Health, Emory UniversityGeisel School of Medicine, Dartmouth CollegeMoffitt Cancer CenterMoffitt Cancer CenterMoffitt Cancer CenterThe University of Texas MD Anderson Cancer CenterThe University of Texas MD Anderson Cancer CenterRollins School of Public Health, Emory UniversityUniversity of South Carolina Arnold School of Public HealthRutgers Cancer InstituteStanford University School of MedicineMelvin and Bren Simon Comprehensive Cancer Center, Indiana UniversityKarmanos Cancer Institute, Wayne State UniversityUniversity of Nebraska Medical CenterUniversity of Tennessee Medical CenterMedical University of South CarolinaDuke University School of MedicineChildren’s Mercy HospitalMoffitt Cancer CenterPopulation Health Sciences, Huntsman Cancer Institute, University of UtahDuke University School of MedicineRollins School of Public Health, Emory UniversityGeisel School of Medicine, Dartmouth CollegeGeisel School of Medicine, Dartmouth CollegeMoffitt Cancer CenterAbstract Introduction Retrotransposons (REs) constitute nearly half of the genome and include long terminal repeat (LTR) elements, Long INterspersed Elements (LINE), and Short INterspersed Elements (SINE). REs are typically silenced in somatic tissues via DNA methylation but can be reactivated through DNA hypomethylation, potentially impacting gene regulation. Here, we investigate genome-scale profiles of RE methylation in high-grade serous ovarian carcinoma (HGSOC) and associations with survival among Black women. Methods Methylation levels of LTR, LINE-1, and Alu (type of SINE) in 200 HGSOC tumors were predicted using a random forest approach and clustered using multiple consensus algorithms. Associations between RE methylation clusters and survival were evaluated using Cox proportional hazard regression, adjusting for age, stage, and debulking status. We performed sensitivity analyses restricted to women with late-stage disease and with adjustment for BRCA1/BRCA2 mutations. Results Two RE methylation clusters were identified. Cluster 1 exhibited a more hypomethylated RE profile (“Active”), while Cluster 2 was more hypermethylated (“Repressed”). No statistically significant differences in patient or clinical characteristics were observed between clusters. Compared to the Active Cluster, the Repressed Cluster was associated with an increased risk of mortality (HR = 2.41; 95% CI 1.04–5.59) and had a lower proportion of T cells. This association was consistent in sensitivity analyses. Conclusion A more hypermethylated RE profile was linked to worse survival among Black women with HGSOC, highlighting the potential of RE methylation as a prognostic biomarker. Further research is needed to understand the underlying biological mechanisms and their implications in ovarian cancer biology and treatment.https://doi.org/10.1186/s13148-025-01942-9 |
| spellingShingle | Christelle Colin-Leitzinger Katherine A. Lawson-Michod Courtney E. Johnson Irma M. Vlasac Sean Yoder Tania Mesa Dana Roeber Chad Huff Michelle A. T. Hildebrandt Kristin Haller Anthony J. Alberg Elisa V. Bandera Melissa Bondy Michele L. Cote Theresa Hastert Edward S. Peters Paul D. Terry Andrew B. Lawson Andrew Berchuck Brooke L. Fridley Jing-Yi Chern Jennifer A. Doherty Jeffrey R. Marks Joellen M. Schildkraut Brock C. Christensen Lucas A. Salas Lauren C. Peres Retrotransposon methylation profiles and survival in Black women with high-grade serous ovarian carcinoma Clinical Epigenetics |
| title | Retrotransposon methylation profiles and survival in Black women with high-grade serous ovarian carcinoma |
| title_full | Retrotransposon methylation profiles and survival in Black women with high-grade serous ovarian carcinoma |
| title_fullStr | Retrotransposon methylation profiles and survival in Black women with high-grade serous ovarian carcinoma |
| title_full_unstemmed | Retrotransposon methylation profiles and survival in Black women with high-grade serous ovarian carcinoma |
| title_short | Retrotransposon methylation profiles and survival in Black women with high-grade serous ovarian carcinoma |
| title_sort | retrotransposon methylation profiles and survival in black women with high grade serous ovarian carcinoma |
| url | https://doi.org/10.1186/s13148-025-01942-9 |
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