期刊
CANCER CELL
卷 37, 期 4, 页码 569-+出版社
CELL PRESS
DOI: 10.1016/j.ccell.2020.03.011
关键词
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资金
- Government of Canada through Genome Canada [OGI-121]
- Ontario Genomics Institute [OGI-121]
- Kid's Brain Tumor Cure
- Brain Tumor Research Assistance and Information Network
- Pediatric Low-Grade Astrocytoma Foundation
- Meagan's Walk
- B.r.a.i.n.child Canada
- Canadian Cancer Society [702296]
- Canadian Institutes of Health Research [159805]
- Garron Family Chair in Childhood Cancer Research at The Hospital for Sick Children
- Canadian Institutes of Health Research (CGS-M) scholarship
- Ontario Graduate Scholarship
- Tokyo Children's Cancer Study Group (TCCSG) scholarship of the Gold Ribbons Network of Japan
- Marie-Josee and Henry R. Kravis Center for Molecular Oncology
- National Cancer Institute Cancer Center Core grant [P30-CA008748]
- American Lebanese Syrian Associated Charities (ALSAC) of St. Jude Children's Research Hospital
Pediatric low-grade gliomas (pLGG) are frequently driven by genetic alterations in the RAS-mitogen-activated protein kinase (RAS/MAPK) pathway yet show unexplained variability in their clinical outcome. To address this, we characterized a cohort of >1,000 clinically annotated pLGG. Eighty-four percent of cases harbored a driver alteration, while those without an identified alteration also often exhibited upregulation of the RAS/MAPK pathway. pLGG could be broadly classified based on their alteration type. Rearrangement-driven tumors were diagnosed at a younger age, enriched for WHO grade I histology, infrequently progressed, and rarely resulted in death as compared with SNV-driven tumors. Further sub-classification of clinical-molecular correlates stratified pLGG into risk categories. These data highlight the biological and clinical differences between pLGG subtypes and opens avenues for future treatment refinement.
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