Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-11493-2
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Funding
- Pediatric Low-Grade Astrocytoma Fund at the Pediatric Brain Tumor Foundation
- Stop and Shop Pediatric Brain Tumor Program
- Conquer Cancer Foundation
- Strike 3 Foundation ASCOYoung Investigator Award
- Michael Mosier Defeat DIPG
- ChadTough Foundation Fellowship
- NIH [PO1CA142536, K99CA201592, R01CA188228, R01CA142536, R01CA219943, F32CA180653, 2U19AI089992, 1U54CA217377, 2P01AI039671, 5U24AI118672, 2RM1HG006193, 1R33CA202820, 2R01HL095791, 1R01AI138546, 1R01HL134539, 1R01DA046277]
- St Baldrick's Foundation
- Friends of DFCI
- Team Jack Foundation
- Andrysiak Fund for LGG
- Jared Branfman Sunflowers For Life Fund For Pediatric Brain And Spinal Cancer Research
- Gray Matters Brain Cancer Foundation
- Ian's Friends Foundation
- Sontag Foundation
- Searle Scholars Program
- Beckman Young Investigator Program
- Pew-tewart Scholars
- Sloan Fellowship in Chemistry
- Bill and Melinda Gates Foundation [OPP1139972, OPP1137006, OPP1116944]
- Bill and Melinda Gates Foundation [OPP1139972, OPP1116944, OPP1137006] Funding Source: Bill and Melinda Gates Foundation
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Pilocytic astrocytoma (PA), the most common childhood brain tumor, is a low-grade glioma with a single driver BRAF rearrangement. Here, we perform scRNAseq in six PAs using methods that enabled detection of the rearrangement. When compared to higher-grade gliomas, a strikingly higher proportion of the PA cancer cells exhibit a differentiated, astrocyte-like phenotype. A smaller proportion of cells exhibit a progenitor-like phenotype with evidence of proliferation. These express a mitogen-activated protein kinase (MAPK) programme that was absent from higher-grade gliomas. Immune cells, especially microglia, comprise 40% of all cells in the PAs and account for differences in bulk expression profiles between tumor locations and subtypes. These data indicate that MAPK signaling is restricted to relatively undifferentiated cancer cells in PA, with implications for investigational therapies directed at this pathway.
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