Details

Autor(en) / Beteiligte

• Ryall, Scott
• Zapotocky, Michal
• Fukuoka, Kohei
• Nobre, Liana
• Guerreiro Stucklin, Ana
• Bennett, Julie
• Siddaway, Robert
• Li, Christopher
• Pajovic, Sanja
• Arnoldo, Anthony
• Kowalski, Paul E.
• Johnson, Monique
• Sheth, Javal
• Lassaletta, Alvaro
• Tatevossian, Ruth G.
• Orisme, Wilda
• Qaddoumi, Ibrahim
• Surrey, Lea F.
• Li, Marilyn M.
• Waanders, Angela J.
• Gilheeney, Stephen
• Rosenblum, Marc
• Bale, Tejus
• Tsang, Derek S.
• Laperriere, Normand
• Kulkarni, Abhaya
• Ibrahim, George M.
• Drake, James
• Dirks, Peter
• Taylor, Michael D.
• Rutka, James T.
• Laughlin, Suzanne
• Shroff, Manohar
• Shago, Mary
• Hazrati, Lili-Naz
• D'Arcy, Colleen
• Ramaswamy, Vijay
• Bartels, Ute
• Huang, Annie
• Bouffet, Eric
• Karajannis, Matthias A.
• Santi, Mariarita
• Ellison, David W.
• Tabori, Uri
• Hawkins, Cynthia

Titel

Integrated Molecular and Clinical Analysis of 1,000 Pediatric Low-Grade Gliomas

Ist Teil von

• Cancer cell, 2020-04, Vol.37 (4), p.569-583.e5

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •KIAA1549-BRAF, BRAF p.V600E, and NF1 mutations account for 2/3 of pLGG•Activation of the RAS/MAPK pathway is nearly universal in pLGG•pLGG comprise two distinct clinical subgroups: rearrangement- or SNV-driven•Risk stratification based on alteration type effectively predicts patient outcome Ryall et al. perform a comprehensive analysis of the molecular underpinnings and clinical correlates of 1000 pediatric low-grade gliomas. They uncover unique clinical features based on the type of molecular alteration identified and provide a risk based stratification to help infer treatment decisions.