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

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

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)569-583.e5
JournalCancer Cell
Volume37
Issue number4
DOIs
StatePublished - Apr 13 2020

Keywords

  • RAS/MAPK pathway
  • brain tumor
  • low-grade glioma
  • molecular diagnostics
  • neurooncology
  • pediatric
  • risk stratification

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Ryall, S., Zapotocky, M., Fukuoka, K., Nobre, L., Guerreiro Stucklin, A., Bennett, J., Siddaway, R., Li, C., Pajovic, S., Arnoldo, A., Kowalski, P. E., Johnson, M., Sheth, J., Lassaletta, A., Tatevossian, R. G., Orisme, W., Qaddoumi, I., Surrey, L. F., Li, M. M., ... Hawkins, C. (2020). Integrated Molecular and Clinical Analysis of 1,000 Pediatric Low-Grade Gliomas. Cancer Cell, 37(4), 569-583.e5. https://doi.org/10.1016/j.ccell.2020.03.011