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• W3109972932 abstract "ABSTRACT Background Osteosarcoma (OSA) is an aggressive malignancy predominantly affecting children and young-adults. Genetic analysis has characterized very few recurrent mutations in OSA, and an improved understanding of interpatient tumor heterogeneity is needed for clinical management. Methods We analyzed genome-wide DNA methylation in primary OSA tumors from the NCI Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program (n = 83) profiled using the Illumina 450K methylation array. We tested if broad genomic methylation predicted outcomes and defined supervised methylomic signatures predictive of Recurrence Free Survival (RFS), Chemotherapy Response (CR), and Metastatic disease at Diagnosis (MetDx). We assessed methylation pattern reproducibility in two independent clinical datasets (n = 28 and 34) and in an in vitro dataset (n = 11). Correlations between genomic methylation and transcription were tested using TARGET RNA-seq data. An in silico pharmacogenomic screen was performed to identify agents for future stratified application. Results Genome-wide methylation defined two subgroups. Relatively hypomethylated tumors experienced better chemotherapy response (Odds Ratio = 6.429, Fisher’s p = 0.007), longer RFS (metastatic, median 2.3 vs 26.7 months, localized, median 63.5 vs 104.7 months, stratified log-rank p = 0.006), and Overall Survival (p = 5×10-4) than hypermethylated tumors. Robust genomic methylation signatures predictive of RFS and CR were defined, and the signatures’ methylation patterns were reproducible in the independent clinical and in vitro datasets. The RFS signature was enriched for intragenic sites, whereas the CR signature and clinically relevant genome-wide methylation patterns were enriched for intergenic sites. Normal-tissue-like methylation patterns were associated with poor prognosis and in vitro analysis suggested that the methylation signatures are associated with tumor aggressiveness. Downstream transcriptional analysis revealed that genes annotated to the RFS methylation signature were also predictive survival. The transcriptional program represented in the RFS signature included several critical cellular pathways, whereas the CR signature was associated with much fewer known pathways, possibly reflecting a much broader cellular “methylation state” related to chemoresponse. A pharmacogenomic screen identified potential therapies, including epigenomic modifiers, for future stratified clinical application. Conclusion Genomic methylation offers insight into patient prognosis and could be a useful tool for developing alternate adjuvant therapeutic strategies." @default.
• W3109972932 created "2020-12-07" @default.
• W3109972932 creator A5004725850 @default.
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• W3109972932 date "2020-11-30" @default.
• W3109972932 modified "2023-10-18" @default.
• W3109972932 title "Genome-wide DNA methylation patterns reveal clinically relevant predictive and prognostic subtypes in osteosarcoma" @default.
• W3109972932 cites W1518200090 @default.
• W3109972932 cites W1854116296 @default.
• W3109972932 cites W1963611189 @default.
• W3109972932 cites W1967532587 @default.
• W3109972932 cites W1998931089 @default.
• W3109972932 cites W2008340135 @default.
• W3109972932 cites W2009727781 @default.
• W3109972932 cites W2010256904 @default.
• W3109972932 cites W2011817173 @default.
• W3109972932 cites W2013275824 @default.
• W3109972932 cites W2029197798 @default.
• W3109972932 cites W2030111741 @default.
• W3109972932 cites W2034910664 @default.
• W3109972932 cites W2048593013 @default.
• W3109972932 cites W2055986128 @default.
• W3109972932 cites W2056040742 @default.
• W3109972932 cites W2056155872 @default.
• W3109972932 cites W2058741514 @default.
• W3109972932 cites W2060688081 @default.
• W3109972932 cites W2061658704 @default.
• W3109972932 cites W2062093164 @default.
• W3109972932 cites W2062455028 @default.
• W3109972932 cites W2063282481 @default.
• W3109972932 cites W2063296278 @default.
• W3109972932 cites W2067011387 @default.
• W3109972932 cites W2068773189 @default.
• W3109972932 cites W2073697204 @default.
• W3109972932 cites W2082371387 @default.
• W3109972932 cites W2084118479 @default.
• W3109972932 cites W2095599995 @default.
• W3109972932 cites W2095734937 @default.
• W3109972932 cites W2100475900 @default.
• W3109972932 cites W2101870168 @default.
• W3109972932 cites W2102330962 @default.
• W3109972932 cites W2108068107 @default.
• W3109972932 cites W2114570899 @default.
• W3109972932 cites W2115160785 @default.
• W3109972932 cites W2118783447 @default.
• W3109972932 cites W2125789330 @default.
• W3109972932 cites W2127192982 @default.
• W3109972932 cites W2127230663 @default.
• W3109972932 cites W2128016314 @default.
• W3109972932 cites W2128146359 @default.
• W3109972932 cites W2128188406 @default.
• W3109972932 cites W2129915465 @default.
• W3109972932 cites W2139619092 @default.
• W3109972932 cites W2143505663 @default.
• W3109972932 cites W2150414518 @default.
• W3109972932 cites W2150926065 @default.
• W3109972932 cites W2151554216 @default.
• W3109972932 cites W2153898423 @default.
• W3109972932 cites W2158217645 @default.
• W3109972932 cites W2158233796 @default.
• W3109972932 cites W2158774461 @default.
• W3109972932 cites W2159955284 @default.
• W3109972932 cites W2165528850 @default.
• W3109972932 cites W2165678358 @default.
• W3109972932 cites W2165948908 @default.
• W3109972932 cites W2166275934 @default.
• W3109972932 cites W2170989872 @default.
• W3109972932 cites W2179438025 @default.
• W3109972932 cites W2213752852 @default.
• W3109972932 cites W2223836536 @default.
• W3109972932 cites W2303408208 @default.
• W3109972932 cites W2323326409 @default.
• W3109972932 cites W2328946792 @default.
• W3109972932 cites W2329218644 @default.
• W3109972932 cites W2344321498 @default.
• W3109972932 cites W2346520135 @default.
• W3109972932 cites W2461427403 @default.
• W3109972932 cites W2513951655 @default.
• W3109972932 cites W2594076746 @default.
• W3109972932 cites W2610474435 @default.
• W3109972932 cites W2616354644 @default.
• W3109972932 cites W2618466351 @default.
• W3109972932 cites W2663574681 @default.
• W3109972932 cites W2732316920 @default.
• W3109972932 cites W2759360483 @default.
• W3109972932 cites W2763192238 @default.
• W3109972932 cites W2783862258 @default.
• W3109972932 cites W2805304375 @default.
• W3109972932 cites W2810908878 @default.
• W3109972932 cites W2811304114 @default.

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