期刊
CLINICAL CANCER RESEARCH
卷 17, 期 14, 页码 4790-4798出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-11-0034
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资金
- Brain tumor Society USA
- Pediatric Brain tumor Foundation USA
- B.R.A.I.Nchild Canada
Purpose: Recent studies have revealed that the majority of pediatric low-grade astrocytomas (PLGA) harbor the BRAF-KIAA1549 (B-K) fusion gene resulting in constitutive activation of the RAS/MAPK pathway. However, the clinical significance of this genetic alteration is yet to be determined. We aimed to test the prognostic role of the B-K fusion in progression of incompletely resected PLGA. Experimental Design: We retrospectively identified 70 consecutive patients with incompletely resected clinically relevant PLGA. We added 76 tumors diagnosed at our institution between 1985 and 2010 as controls. We examined BRAF alterations by reverse transcriptase PCR, FISH, and single-nucleotide polymorphism array analysis and correlated that with progression-free survival (PFS). Results: Overall, 60% of tumors were B-K fusion positive. All patients with B-K fused PLGA are still alive. Five-year PFS was 61% +/- 8% and 18% +/- 8% for fusion positive and negative patients, respectively (P = 0.0004). B-K fusion resulted in similarly significant favorable PFS for patients who received chemotherapy. Multivariate analysis revealed that B-K fusion was the most significant favorable prognostic factor in incompletely resected PLGA and was independent of location, pathology, and age. In vitro, BRAF overexpression resulted in growth arrest associated with DNA damage (gamma H2AX expression). Five-year PFS was 68% +/- 15% and 0% for patients with B-K fused and gamma H2AX-expressing PLGA versus negative tumors (P = 0.001). Conclusion: These data suggest that B-K fusion confers a less aggressive clinical phenotype on PLGA and may explain their tendency to growth arrest. Combined analysis of B-K fusion and gamma H2AX expression can determine prognosis and may be a powerful tool to tailor therapy for these patients. Clin Cancer Res; 17(14); 4790-8. (C)2011 AACR.
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