TY - JOUR
T1 - Retrotransposon methylation profiles and survival in Black women with high-grade serous ovarian carcinoma
AU - Colin-Leitzinger, Christelle
AU - Lawson-Michod, Katherine A.
AU - Johnson, Courtney E.
AU - Vlasac, Irma M.
AU - Yoder, Sean
AU - Mesa, Tania
AU - Roeber, Dana
AU - Huff, Chad
AU - Hildebrandt, Michelle A.T.
AU - Haller, Kristin
AU - Alberg, Anthony J.
AU - Bandera, Elisa V.
AU - Bondy, Melissa
AU - Cote, Michele L.
AU - Hastert, Theresa
AU - Peters, Edward S.
AU - Terry, Paul D.
AU - Lawson, Andrew B.
AU - Berchuck, Andrew
AU - Fridley, Brooke L.
AU - Chern, Jing Yi
AU - Doherty, Jennifer A.
AU - Marks, Jeffrey R.
AU - Schildkraut, Joellen M.
AU - Christensen, Brock C.
AU - Salas, Lucas A.
AU - Peres, Lauren C.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105012125504
UR - https://www.scopus.com/pages/publications/105012125504#tab=citedBy
U2 - 10.1186/s13148-025-01942-9
DO - 10.1186/s13148-025-01942-9
M3 - Article
C2 - 40734190
AN - SCOPUS:105012125504
SN - 1868-7075
VL - 17
JO - Clinical epigenetics
JF - Clinical epigenetics
IS - 1
M1 - 134
ER -