| Literature DB >> 32289278 |
Scott Ryall1, Michal Zapotocky2, Kohei Fukuoka3, Liana Nobre3, Ana Guerreiro Stucklin4, Julie Bennett3, Robert Siddaway5, Christopher Li1, Sanja Pajovic5, Anthony Arnoldo6, Paul E Kowalski6, Monique Johnson6, Javal Sheth7, Alvaro Lassaletta8, Ruth G Tatevossian9, Wilda Orisme9, Ibrahim Qaddoumi10, Lea F Surrey11, Marilyn M Li12, Angela J Waanders13, Stephen Gilheeney14, Marc Rosenblum15, Tejus Bale15, Derek S Tsang16, Normand Laperriere16, Abhaya Kulkarni17, George M Ibrahim17, James Drake17, Peter Dirks18, Michael D Taylor18, James T Rutka18, Suzanne Laughlin19, Manohar Shroff19, Mary Shago20, Lili-Naz Hazrati21, Colleen D'Arcy22, Vijay Ramaswamy23, Ute Bartels24, Annie Huang25, Eric Bouffet24, Matthias A Karajannis14, Mariarita Santi11, David W Ellison9, Uri Tabori26, Cynthia Hawkins27.
Abstract
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.Entities:
Keywords: RAS/MAPK pathway; brain tumor; low-grade glioma; molecular diagnostics; neurooncology; pediatric; risk stratification
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Year: 2020 PMID： 32289278 PMCID： PMC7169997 DOI： 10.1016/j.ccell.2020.03.011
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743