Therapeutic and prognostic implications of BRAF V600E in pediatric low-grade gliomas

Alvaro Lassaletta, Michal Zapotocky, Matthew Mistry, Vijay Ramaswamy, Marion Honnorat, Rahul Krishnatry, Ana Guerreiro Stucklin, Nataliya Zhukova, Anthony Arnoldo, Scott Ryall, Catriona Ling, Tara McKeown, Jim Loukides, Ofelia Cruz, Carmen De Torres, Cheng Ying Ho, Roger J. Packer, Ruth Tatevossian, Ibrahim Qaddoumi, Julie H. HarreldJames D. Dalton, Jean Mulcahy-Levy, Nicholas Foreman, Matthias A. Karajannis, Shiyang Wang, Matija Snuderl, Amulya Nageswara Rao, Caterina Giannini, Mark Kieran, Keith L. Ligon, Maria Luisa Garre, Paolo Nozza, Samantha Mascelli, Alessandro Raso, Sabine Mueller, Theodore Nicolaides, Karen Silva, Romain Perbet, Alexandre Vasiljevic, Cécile Faure Conter, Didier Frappaz, Sarah Leary, Courtney Crane, Aden Chan, Ho Keung Ng, Zhi Feng Shi, Ying Mao, Elizabeth Finch, David Eisenstat, Bev Wilson, Anne Sophie Carret, Peter Hauser, David Sumerauer, Lenka Krskova, Valerie Larouche, Adam Fleming, Shayna Zelcer, Nada Jabado, James T. Rutka, Peter Dirks, Michael D. Taylor, Shiyi Chen, Ute Bartels, Annie Huang, David W. Ellison, Eric Bouffet, Cynthia Hawkins, Uri Tabori

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109 Scopus citations


Purpose: BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods: A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180). Results: BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a broad spectrum of histologies and sites, including midline locations, which are not often routinely biopsied in clinical practice. Patients with BRAF V600E PLGG exhibited poor outcomes after chemotherapy and radiation therapies that resulted in a 10-year progression-free survival of 27% (95% CI, 12.1% to 41.9%) and 60.2% (95% CI, 53.3% to 67.1%) for BRAF V600E and wild-type PLGG, respectively (P < .001). Additional multivariable clinical and molecular stratification revealed that the extent of resection and CDKN2A deletion contributed independently to poor outcome in BRAF V600E PLGG. A similar independent role for CDKN2A and resection on outcome were observed in the independent cohort. Quantitative imaging analysis revealed progressive disease and a lack of response to conventional chemotherapy in most patients with BRAF V600E PLGG. Conclusion: BRAF V600E PLGG constitutes a distinct entity with poor prognosis when treated with current adjuvant therapy.

Original languageEnglish (US)
Pages (from-to)2934-2941
Number of pages8
JournalJournal of Clinical Oncology
Issue number25
StatePublished - Sep 1 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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