MYC Regulates a DNA Repair Gene Expression Program in Small Cell Carcinoma of the Ovary, Hypercalcemic Type.
James R Evans, Jing Wang, Cinthia N Reed, Joy H Creighton, Kaylee B Garrison, Abigail N Robertson, Ashley Lira-Rivera, Diondre' D Baisden, William P Tansey, Rafet Al-Tobasei and 3 more
Article in Cancers, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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13 authors.
James R EvansDepartment of Biology, Middle Tennessee State University, Murfreesboro, TN 37132, USA.ORCID 0009-0004-7435-2874
Jing WangCenter for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Cinthia N ReedDepartment of Biology, Middle Tennessee State University, Murfreesboro, TN 37132, USA.
Joy H CreightonDepartment of Biology, Middle Tennessee State University, Murfreesboro, TN 37132, USA.
Kaylee B GarrisonDepartment of Biology, Middle Tennessee State University, Murfreesboro, TN 37132, USA.
Abigail N RobertsonDepartment of Biology, Middle Tennessee State University, Murfreesboro, TN 37132, USA.
Ashley Lira-RiveraDepartment of Biology, Middle Tennessee State University, Murfreesboro, TN 37132, USA.
Diondre' D BaisdenDepartment of Biology, Middle Tennessee State University, Murfreesboro, TN 37132, USA.
William P TanseyDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37240, USA.ORCID 0000-0002-3900-0978
Rafet Al-TobaseiDepartment of Computer Science, Middle Tennessee State University, Murfreesboro, TN 37132, USA.ORCID 0000-0002-0578-0734
Jessica D LangDepartment of Pathology & Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.ORCID 0000-0001-9700-4785
Qi LiuCenter for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
April M WeissmillerDepartment of Biology, Middle Tennessee State University, Murfreesboro, TN 37132, USA.ORCID 0000-0003-4505-0530
Funding
Vanderbilt-Ingram Cancer Center SPORE in Gastrointestinal CancerP50CA236733 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2019 to 2026
$19.6M
The Tumor Suppressor Role of SMARCA4 in SCCOHTR01CA195670 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HUNTSMAN, DAVID, TRENT, JEFFREY M. · 2015 to 2019
$3.7M
The MYC-SWI/SNF connection in rhabdoid tumorsR01CA247833 · NCI · VANDERBILT UNIVERSITY · PI TANSEY, WILLIAM PATRICK · 2020 to 2024
$1.8M
Characterization of the role of super-enhancers in ovarian cancer treatment responseR00CA234391 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI LANG, JESSICA DIANE · 2021 to 2023
$744k
Characterization of the role of super-enhancers in ovarian cancer treatment responseK99CA234391 · NCI · TRANSLATIONAL GENOMICS RESEARCH INST · PI LANG, JESSICA DIANE · 2019 to 2020
$223k
Exposing the role of MYC in small cell carcinoma of the ovary hypercalcemic typeR03CA273609 · NCI · MIDDLE TENNESSEE STATE UNIVERSITY · PI WEISSMILLER, APRIL M. · 2023 to 2024
objectivesSCCOHT is an aggressive and often fatal cancer that belongs to the ~20% of cancers defined by mutations to subunits of the SWI/SNF chromatin remodeling complex. In SCCOHT, mutations to the
methodsIn this study, we investigate the contribution of MYC to SCCOHT biology by performing a combination of chromatin binding and transcriptome assays in genetically engineered SCCOHT cell lines, with subsequent validation using patient tumor expression data.
resultsWe find that MYC binds to thousands of active promoters in the BIN-67 SCCOHT cell line and that the depletion of MYC results in a broad range of gene expression changes with a notable effect on the expression of genes related to DNA repair. We uncover an MYC-regulated DNA repair gene expression program in BIN-67 cells that is antagonized by BRG1 reintroduction. Finally, we identify a DNA repair gene signature that is upregulated in SCCOHT tumors and in tumors defined by loss of the SWI/SNF subunit SNF5.
conclusionsCollectively, these data implicate MYC as a robust regulator of DNA repair gene expression in SCCOHT and lay a foundation for future studies focused on interrogating the relationship between BRG1 and MYC.
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MYC Regulates a DNA Repair Gene Expression Program in Small Cell Carcinoma of the Ovary, Hypercalcemic Type. · full record | OpenQuestion