LGG-53. Evaluation of KIAA-BRAF1549 fusions in pilocytic astrocytoma with clinicopathological correlation

BACKGROUND: Pilocytic astrocytomas (PAs) are the primary tumors most frequently found in children and adolescents, accounting for 5.4% of all gliomas. The overall prognosis of PAs is good, yet a substantial no of cases have a poor outcome, with recurrence, and ultimately death. The KIAA1549-BRAF fusion is a useful putative diagnostic marker for PAs and BRAF also is an important therapeutic marker. AIM AND OBJECTIVES: To study the frequency of KIAA1549-BRAF fusion (16-9, 15-9 and 16-11) in different locations of PAs using qRT-PCR technique in FFPE samples. METHODOLOGY: Three different exon rearrangements of KIAA1549-BRAF (16-9, 15-9 and 16-11) fusions were assessed in 50 cases of PAs by using qRT-PCR (gold standard). FISH assay was also performed in all the cases. RESULTS: Out of 50 PAs, 32 were localised in midline structures such as the cerebellum, optic pathway, hypothalamus, and brain stem while 18 in non-midline regions like the cerebral hemispheres. Majority of the cases (35/50); 70% were positive for KIAA1549-BRAF fusion by RT-PCR. Of these, (16/35); 45.7% harboured 15-9 fusion, (15/35); 42.8% harboured 16-9 fusion, and only (4/35); 11.4% had 16-11 fusion. Only (24/30); 48% KIAA1549-BRAF showed fusion by FISH assay. There was 54.2% concordance between FISH and RT-PCR results. KIAA1549-BRAF fusion was observed in 78% of midline and 55.5% of non-midline cases. The frequency of KIAA1549-BRAF fusion decreased with increasing age, 77% in the age group <20, 54% in the age group 20-40 and 30% in the age group >40. CONCLUSION: 15-9 and 16-9 KIAA1549-BRAF were the most frequently occurring fusions dominantly seen in the midline. The presence of fusion is inversely proportional to the age of patients. qRT-PCR is the gold standard technique and FISH assay has moderate concordance with qRT-PCR platform.