BRAF Alterations

BRAF alterations (fusion or mutation)
in the MAPK pathway

Lily, lives with pLGG.
Lives for dancing.

The MAPK pathway is a key regulator of cell proliferation, survival, and differentiation6

  • In normal cells, the pathway is tightly regulated. BRAF is activated by RAS and relays signals via MEK and ERK7

  • However, when BRAF is altered, the pathway is unregulated, leading to increased, continuous signaling, independent of RAS. This can occur from a BRAF gene fusion or point mutation6-8

Explore BRAF in the MAPK pathway for pediatric low-grade glioma (pLGG)

Activating BRAF alterations are the most common oncogenic driver of pLGG3

Up to 75% of pLGG have a BRAF alteration (fusion or mutation). Of these, approximately 80% have a BRAF fusion, while approximately 20% have a BRAF point mutation.9-13

BRAF-altered pLGG9-13

Infographics of pie chart percentages of pLGGs with BRAF fusions and mutations. Up to 75% of pLGGs are BRAF-altered. Incidence of BRAF alterations varies across pLGG subtypes. Of those with a BRAF alteration, nearly 80% have a BRAF fusion, predominantly seen in pilocytic astrocytomas. Nearly 20% have a BRAF point mutation. These may vary across subtypes.
Infographics of pie chart percentages of pLGGs with BRAF fusions and mutations. Up to 75% of pLGGs are BRAF-altered. Incidence of BRAF alterations varies across pLGG subtypes. Of those with a BRAF alteration, nearly 80% have a BRAF fusion, predominantly seen in pilocytic astrocytomas. Nearly 20% have a BRAF point mutation. These may vary across subtypes.

Knowing if your patient’s pLGG harbors a BRAF fusion or point mutation is critical as it may help determine an appropriate targeted therapy.4

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Treatment Landscape

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References: 1. Hauser P. Classification and treatment of pediatric gliomas in the molecular era. Children (Basel). 2021;8(9):739. doi:10.3390/children8090739 2. Louis DN, Perry A, Wesseling P, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol. 2021;23(8):1231-1251. doi:10.1093/neuonc/noab106 3. Ryall S, Tabori U, Hawkins C. Pediatric low-grade glioma in the era of molecular diagnostics. Acta Neuropathol Commun. 2020;8(1):30. doi:100.1186/s40478-020-00902-z 4. Behling F, Schittenhelm J. Oncogenic BRAF alterations and their role in brain tumors. Cancers (Basel). 2019;11(6):794. doi:10.3390/cancers11060794 5. Andrews LJ, Thornton ZA, Saincher SS. Prevalence of BRAF V600E in glioma and use of BRAF inhibitors in patients with BRAF V600E mutation-positive glioma: systemic review. Neuro Oncol. 2022; 24(4):528-540. doi:10.1093/neuonc/noab247 6. Sholl LM. A narrative review of BRAF alterations in human tumors: diagnostic and predictive implications. Precis Cancer Med. 2020; 3(26);1-15. doi: 10.21037/pcm-20-39 7. Yaeger R, Corcoran RB. Targeting alterations in the RAF-MEK pathway. Cancer Discov. 2019;9(3):329-341. doi:10.1158/2159-8290.CD-18-1321 8. Srinivasa K, Cross KA, Dahiya S. BRAF alterations in central and peripheral nervous system tumors. Front Oncol. 2020;10:574974. doi:10.3389/fonc.2020.574974 9. Sun Y, Alberta JA, Pilarz C. A brain-penetrant RAF dimer antagonist for the noncanonical BRAF oncoprotein of pediatric low-grade astrocytomas. Neuro Oncol. 2017;19(6):774-785. doi:10.1093/neuonc/now261 10. Penman CL, Faulkner C, Lowis SP, Kurian KM. Current understanding of BRAF alterations in diagnosis, prognosis, and therapeutic targeting in pediatric low-grade gliomas. Front Oncol. 2015;5:54. doi:10.3389/fonc.2015.00054 11. Ryall S, Zapotocky M, Fukuoka K, et al. Integrated molecular and clinical analysis of 1,000 pediatric low-grade gliomas. Cancer Cell. 2020;37(4):569-583.e5. doi:10.1016/j.ccell.2020.03.011 12. Cohen AR. Brain tumors in children. N Engl J Med. 2020; 386(20):1922-1931. doi:10.1056/NEJMra2116344 13. Lassaletta A, Zapotocky M, Mistry M, et al. Therapeutic and prognostic implications of BRAF V600E in pediatric low-grade gliomas. J Clin Oncol. 2017;35(25):2934-2941. doi:10.1200/JCO.2016.71.8726