GE-03 * HIGH RATE OF CONCURRENT BRAF-KIAA1549 GENE FUSION AND 1p DELETION IN DISSEMINATED OLIGODENDROGLIAL-LIKE LEPTOMENINGEAL TUMORS

Abstract

INTRODUCTION: Activating fusions of the serine-threonine-kinase-encoding BRAF gene with the nearby gene KIAA1549 have been described in low-grade pediatric brain tumors, including most cerebellar pilocytic astrocytomas and smaller numbers of other, generally low-grade, CNS tumors. Disseminated oligodendroglial-like leptomeningeal tumors (DOLTs) are slowly progressive pediatric tumors with limited, if any parenchymal involvement. In this series, we assessed the status of BRAF-KIAA1549 and chromosomes 1p and 19q, with deletions of the latter known to variably occur in this tumor type. METHODS: 20 archival DOLTs were examined by FISH for BRAF-KIAA1549 fusion, and 17 cases for deletions of 1p and 19q. One case was additionally interrogated by SNP-array. Testing for BRAF-V600E mutation was also performed in nine cases. RESULTS: Of 14 informative cases for BRAF-KIAA1549, 9 were fusion positive by FISH, and one harbored a duplication by SNP-array suggestive of the gene fusion, for a total of 10 of 14 positive cases (71%). FISH revealed loss of 1p in 10/17 cases (59%), with 3 of those also being co-deleted for 19q (18%). Of the 10 cases with BRAF fusions, 8 had 1p deletion (80%) and 1 had 19q co-deletion (10%). None of 9 tested specimens were positive for BRAF-V600E mutation. CONCLUSION: These findings indicate a high rate of concurrent BRAF-KIAA1549 gene fusions and 1p deletions in DOLTs. Although BRAF fusions are typical of pilocytic astrocytomas, 1p deletions are not, confirming that DOLTs are pathologically and genetically distinct. These findings also further separate these oligodendroglial-like tumors from adult oligodendrogliomas, although some overlap remains since 1p19 codeletion is occasionally found in DOLT and rare BRAF fusions have been recently reported in otherwise classic, 1p19q codeleted oligodendroglioma.