BRAF rearrangements and BRAF V600E point mutations are recurring events in pediatric low-grade gliomas. However, their clinical significance, including possible interactions between these markers and other glioma biomarkers, is unclear. In this study a retrospective cohort of 198 pediatric low-grade gliomas (including 40 treated with adjuvant therapy) was analyzed for BRAF rearrangements, BRAF V600E, p16/CDKN2A deletion, p53 expression, and MIB1 proliferation index. In tumors with BRAF rearrangement, homozygous p16 deletion correlated with shorter PFS (P = 0.04). High MIB1 proliferation index strongly trended toward correlating with worse response to adjuvant therapy (P = 0.06). On multivariate analyses, the two most consistently powerful independent adverse prognostic markers were midline location (P = 0.0001) and p16 deletion (P = 0.03). Tumors with BRAF V600E had a strong trend toward an increased risk for progression (hazard ratio = 2.48, P = 0.07), whereas those with BRAF rearrangement had a milder trend toward reduced risk (hazard ratio = 0.54, P = 0.15). These data suggest that p16 deletion adversely impacts the outcomes of BRAF-driven gliomas; that high proliferation index may be a better marker of progression risk than BRAF; that BRAF rearrangement and BRAF V600E might not necessarily produce comparable outcomes; and that none of these markers is stronger than tumor location in determining prognosis in pediatric low-grade gliomas.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5558. doi:1538-7445.AM2012-5558