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- W2918054297 abstract "Abstract There is a critical need to improve our understanding of the pathogenesis of melanoma brain metastases (MBM). Thus, we performed RNA sequencing on 88 resected MBMs and 42 patient-matched extracranial metastases; tumors with sufficient tissue also underwent whole-exome sequencing, T-cell receptor sequencing, and IHC. MBMs demonstrated heterogeneity of immune infiltrates that correlated with prior radiation and post-craniotomy survival. Comparison with patient-matched extracranial metastases identified significant immunosuppression and enrichment of oxidative phosphorylation (OXPHOS) in MBMs. Gene-expression analysis of intracranial and subcutaneous xenografts, and a spontaneous MBM model, confirmed increased OXPHOS gene expression in MBMs, which was also detected by direct metabolite profiling and [U-13C]-glucose tracing in vivo. IACS-010759, an OXPHOS inhibitor currently in early-phase clinical trials, improved survival of mice bearing MAPK inhibitor–resistant intracranial melanoma xenografts and inhibited MBM formation in the spontaneous MBM model. The results provide new insights into the pathogenesis and therapeutic resistance of MBMs. Significance: Improving our understanding of the pathogenesis of MBMs will facilitate the rational development and prioritization of new therapeutic strategies. This study reports the most comprehensive molecular profiling of patient-matched MBMs and extracranial metastases to date. The data provide new insights into MBM biology and therapeutic resistance. See related commentary by Egelston and Margolin, p. 581. This article is highlighted in the In This Issue feature, p. 565" @default.
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- W2918054297 date "2019-05-01" @default.
- W2918054297 modified "2023-10-11" @default.
- W2918054297 title "Molecular Profiling Reveals Unique Immune and Metabolic Features of Melanoma Brain Metastases" @default.
- W2918054297 cites W1498931318 @default.
- W2918054297 cites W1862638437 @default.
- W2918054297 cites W1895813995 @default.
- W2918054297 cites W1950829641 @default.
- W2918054297 cites W1951090871 @default.
- W2918054297 cites W1969082125 @default.
- W2918054297 cites W1974499786 @default.
- W2918054297 cites W1986313985 @default.
- W2918054297 cites W2001256455 @default.
- W2918054297 cites W2028092387 @default.
- W2918054297 cites W2031757213 @default.
- W2918054297 cites W2033708806 @default.
- W2918054297 cites W2039123767 @default.
- W2918054297 cites W2048030330 @default.
- W2918054297 cites W2055901890 @default.
- W2918054297 cites W2057893793 @default.
- W2918054297 cites W2086434836 @default.
- W2918054297 cites W2098395271 @default.
- W2918054297 cites W2101774229 @default.
- W2918054297 cites W2104697581 @default.
- W2918054297 cites W2107429737 @default.
- W2918054297 cites W2121886536 @default.
- W2918054297 cites W2121964616 @default.
- W2918054297 cites W2127437403 @default.
- W2918054297 cites W2130430382 @default.
- W2918054297 cites W2133732784 @default.
- W2918054297 cites W2134878419 @default.
- W2918054297 cites W2142020296 @default.
- W2918054297 cites W2156078931 @default.
- W2918054297 cites W2160571820 @default.
- W2918054297 cites W2169465106 @default.
- W2918054297 cites W2175940415 @default.
- W2918054297 cites W2177518191 @default.
- W2918054297 cites W2201379305 @default.
- W2918054297 cites W2326574449 @default.
- W2918054297 cites W2338494814 @default.
- W2918054297 cites W2363164936 @default.
- W2918054297 cites W2405976160 @default.
- W2918054297 cites W2416791964 @default.
- W2918054297 cites W2417761579 @default.
- W2918054297 cites W2435243879 @default.
- W2918054297 cites W2482589824 @default.
- W2918054297 cites W2533508881 @default.
- W2918054297 cites W2551317550 @default.
- W2918054297 cites W2560185130 @default.
- W2918054297 cites W2564115474 @default.
- W2918054297 cites W2598321022 @default.
- W2918054297 cites W2606711458 @default.
- W2918054297 cites W2612541259 @default.
- W2918054297 cites W2620651944 @default.
- W2918054297 cites W2624275086 @default.
- W2918054297 cites W2739338441 @default.
- W2918054297 cites W2753432434 @default.
- W2918054297 cites W2763979809 @default.
- W2918054297 cites W2771485688 @default.
- W2918054297 cites W2806128074 @default.
- W2918054297 cites W2808404256 @default.
- W2918054297 cites W2809965878 @default.
- W2918054297 cites W2888298425 @default.
- W2918054297 cites W2889237222 @default.