DNA methylation and transcriptomic features are preserved throughout disease recurrence and chemoresistance in high grade serous ovarian cancers
Abstract Background Little is known about the role of global DNA methylation in recurrence and chemoresistance of high grade serous ovarian cancer (HGSOC). Methods We performed whole genome bisulfite sequencing and transcriptome sequencing in 62 primary and recurrent tumors from 28 patients with sta...
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BMC
2022-07-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
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| Online Access: | https://doi.org/10.1186/s13046-022-02440-z |
| _version_ | 1818018500074012672 |
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| author | Nicole Gull Michelle R. Jones Pei-Chen Peng Simon G. Coetzee Tiago C. Silva Jasmine T. Plummer Alberto Luiz P. Reyes Brian D. Davis Stephanie S. Chen Kate Lawrenson Jenny Lester Christine Walsh Bobbie J. Rimel Andrew J. Li Ilana Cass Yonatan Berg John-Paul B. Govindavari Joanna K. L. Rutgers Benjamin P. Berman Beth Y. Karlan Simon A. Gayther |
| author_facet | Nicole Gull Michelle R. Jones Pei-Chen Peng Simon G. Coetzee Tiago C. Silva Jasmine T. Plummer Alberto Luiz P. Reyes Brian D. Davis Stephanie S. Chen Kate Lawrenson Jenny Lester Christine Walsh Bobbie J. Rimel Andrew J. Li Ilana Cass Yonatan Berg John-Paul B. Govindavari Joanna K. L. Rutgers Benjamin P. Berman Beth Y. Karlan Simon A. Gayther |
| author_sort | Nicole Gull |
| collection | DOAJ |
| description | Abstract Background Little is known about the role of global DNA methylation in recurrence and chemoresistance of high grade serous ovarian cancer (HGSOC). Methods We performed whole genome bisulfite sequencing and transcriptome sequencing in 62 primary and recurrent tumors from 28 patients with stage III/IV HGSOC, of which 11 patients carried germline, pathogenic BRCA1 and/or BRCA2 mutations. Results Landscapes of genome-wide methylation (on average 24.2 million CpGs per tumor) and transcriptomes in primary and recurrent tumors showed extensive heterogeneity between patients but were highly preserved in tumors from the same patient. We identified significant differences in the burden of differentially methylated regions (DMRs) in tumors from BRCA1/2 compared to non-BRCA1/2 carriers (mean 659 DMRs and 388 DMRs in paired comparisons respectively). We identified overexpression of immune pathways in BRCA1/2 carriers compared to non-carriers, implicating an increased immune response in improved survival (P = 0.006) in these BRCA1/2 carriers. Conclusion These findings indicate methylome and gene expression programs established in the primary tumor are conserved throughout disease progression, even after extensive chemotherapy treatment, and that changes in methylation and gene expression are unlikely to serve as drivers for chemoresistance in HGSOC. |
| first_indexed | 2024-04-14T07:40:18Z |
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| id | doaj.art-3ce2b3a2d5ca4a3c8214cbe45d7c1b40 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-14T07:40:18Z |
| publishDate | 2022-07-01 |
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| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-3ce2b3a2d5ca4a3c8214cbe45d7c1b402022-12-22T02:05:31ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662022-07-0141111810.1186/s13046-022-02440-zDNA methylation and transcriptomic features are preserved throughout disease recurrence and chemoresistance in high grade serous ovarian cancersNicole Gull0Michelle R. Jones1Pei-Chen Peng2Simon G. Coetzee3Tiago C. Silva4Jasmine T. Plummer5Alberto Luiz P. Reyes6Brian D. Davis7Stephanie S. Chen8Kate Lawrenson9Jenny Lester10Christine Walsh11Bobbie J. Rimel12Andrew J. Li13Ilana Cass14Yonatan Berg15John-Paul B. Govindavari16Joanna K. L. Rutgers17Benjamin P. Berman18Beth Y. Karlan19Simon A. Gayther20Department of Biomedical Sciences, Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical CenterDepartment of Biomedical Sciences, Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical CenterDepartment of Biomedical Sciences, Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical CenterDepartment of Biomedical Sciences, Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical CenterDivision of Biostatistics, Department of Public Health Sciences, University of Miami, Miller School of MedicineDepartment of Biomedical Sciences, Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical CenterDepartment of Biomedical Sciences, Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical CenterDepartment of Biomedical Sciences, Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical CenterDepartment of Biomedical Sciences, Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical CenterDepartment of Biomedical Sciences, Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical CenterWomen’s Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical CenterWomen’s Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical CenterWomen’s Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical CenterWomen’s Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical CenterDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Dartmouth-Hitchcock Medical CenterDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical SchoolDepartment of Pathology, Cedars-Sinai Medical CenterDepartment of Pathology, Cedars-Sinai Medical CenterDepartment of Biomedical Sciences, Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical CenterWomen’s Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical CenterDepartment of Biomedical Sciences, Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical CenterAbstract Background Little is known about the role of global DNA methylation in recurrence and chemoresistance of high grade serous ovarian cancer (HGSOC). Methods We performed whole genome bisulfite sequencing and transcriptome sequencing in 62 primary and recurrent tumors from 28 patients with stage III/IV HGSOC, of which 11 patients carried germline, pathogenic BRCA1 and/or BRCA2 mutations. Results Landscapes of genome-wide methylation (on average 24.2 million CpGs per tumor) and transcriptomes in primary and recurrent tumors showed extensive heterogeneity between patients but were highly preserved in tumors from the same patient. We identified significant differences in the burden of differentially methylated regions (DMRs) in tumors from BRCA1/2 compared to non-BRCA1/2 carriers (mean 659 DMRs and 388 DMRs in paired comparisons respectively). We identified overexpression of immune pathways in BRCA1/2 carriers compared to non-carriers, implicating an increased immune response in improved survival (P = 0.006) in these BRCA1/2 carriers. Conclusion These findings indicate methylome and gene expression programs established in the primary tumor are conserved throughout disease progression, even after extensive chemotherapy treatment, and that changes in methylation and gene expression are unlikely to serve as drivers for chemoresistance in HGSOC.https://doi.org/10.1186/s13046-022-02440-zHigh grade serous ovarian cancerMethylationChemoresistanceEpigeneticsWhole genome bisulfite sequencingComputational methods |
| spellingShingle | Nicole Gull Michelle R. Jones Pei-Chen Peng Simon G. Coetzee Tiago C. Silva Jasmine T. Plummer Alberto Luiz P. Reyes Brian D. Davis Stephanie S. Chen Kate Lawrenson Jenny Lester Christine Walsh Bobbie J. Rimel Andrew J. Li Ilana Cass Yonatan Berg John-Paul B. Govindavari Joanna K. L. Rutgers Benjamin P. Berman Beth Y. Karlan Simon A. Gayther DNA methylation and transcriptomic features are preserved throughout disease recurrence and chemoresistance in high grade serous ovarian cancers Journal of Experimental & Clinical Cancer Research High grade serous ovarian cancer Methylation Chemoresistance Epigenetics Whole genome bisulfite sequencing Computational methods |
| title | DNA methylation and transcriptomic features are preserved throughout disease recurrence and chemoresistance in high grade serous ovarian cancers |
| title_full | DNA methylation and transcriptomic features are preserved throughout disease recurrence and chemoresistance in high grade serous ovarian cancers |
| title_fullStr | DNA methylation and transcriptomic features are preserved throughout disease recurrence and chemoresistance in high grade serous ovarian cancers |
| title_full_unstemmed | DNA methylation and transcriptomic features are preserved throughout disease recurrence and chemoresistance in high grade serous ovarian cancers |
| title_short | DNA methylation and transcriptomic features are preserved throughout disease recurrence and chemoresistance in high grade serous ovarian cancers |
| title_sort | dna methylation and transcriptomic features are preserved throughout disease recurrence and chemoresistance in high grade serous ovarian cancers |
| topic | High grade serous ovarian cancer Methylation Chemoresistance Epigenetics Whole genome bisulfite sequencing Computational methods |
| url | https://doi.org/10.1186/s13046-022-02440-z |
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