دورية أكاديمية
Genome-wide DNA methylation patterns reveal clinically relevant predictive and prognostic subtypes in human osteosarcoma
| العنوان: | Genome-wide DNA methylation patterns reveal clinically relevant predictive and prognostic subtypes in human osteosarcoma |
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| المؤلفون: | Lietz, Christopher E., Newman, Erik T., Kelly, Andrew D., Xiang, David H., Zhang, Ziying, Luscko, Caroline A., Lozano-Calderon, Santiago A., Ebb, David H., Raskin, Kevin A., Cote, Gregory M., Choy, Edwin, Nielsen, G. Petur, Haibe-Kains, Benjamin, Aryee, Martin J., Spentzos, Dimitrios |
| المساهمون: | U.S. Department of Health & Human Services | National Institutes of Health, Casper Colson Philanthropic fund Amy Chase McMahon Sarcoma Research Fund |
| المصدر: | Communications Biology ; volume 5, issue 1 ; ISSN 2399-3642 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology, Medicine (miscellaneous) |
| الوصف: | Aberrant methylation of genomic DNA has been reported in many cancers. Specific DNA methylation patterns have been shown to provide clinically useful prognostic information and define molecular disease subtypes with different response to therapy and long-term outcome. Osteosarcoma is an aggressive malignancy for which approximately half of tumors recur following standard combined surgical resection and chemotherapy. No accepted prognostic factor save tumor necrosis in response to adjuvant therapy currently exists, and traditional genomic studies have thus far failed to identify meaningful clinical associations. We studied the genome-wide methylation state of primary tumors and tested how they predict patient outcomes. We discovered relative genomic hypomethylation to be strongly predictive of response to standard chemotherapy. Recurrence and survival were also associated with genomic methylation, but through more site-specific patterns. Furthermore, the methylation patterns were reproducible in three small independent clinical datasets. Downstream transcriptional, in vitro, and pharmacogenomic analysis provides insight into the clinical translation of the methylation patterns. Our findings suggest the assessment of genomic methylation may represent a strategy for stratifying patients for the application of alternative therapies. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s42003-022-03117-1 |
| الإتاحة: | https://doi.org/10.1038/s42003-022-03117-1Test https://www.nature.com/articles/s42003-022-03117-1.pdfTest https://www.nature.com/articles/s42003-022-03117-1Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.73389C4B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s42003-022-03117-1 |
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