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1765 Hemangioblastoma: A Targeted Next Generation Sequencing Study Esther C Yoon, Jian Zhuge, George Kleinman, John T Fallon, Minghao Zhong. New York Medical College at Westchester Medical Center, Valhalla, NY. Background: Hemangioblastomas (HB) are rare CNS tumors and up to 25 % are associated with von Hippel-Lindau syndrome and biallelic inactivation of VHL genes is an important mechanism for pathogenesis. Same mutation is also seen in clear cell renal cell carcinoma (ccRCC) and part explains the overlap of histomorphological and immunohistochemical characteristics. However, molecular difference between the ccRCC and HB are not yet extensively studied. In this study we looked at common gene mutations by targeted NGS in HB and compared to those in ccRCC. Design: Our study composed of two sections: 1) analysis of targeted genetic sequence and 2) study of expression of CAIX in hemangioblastoma by IHC and correlate with VHL mutation status. Five cases of hemangioblastom from elderly patients (mean = 53) with no known family history of VHL disease were selected. Macrodissection of formalin-fixed paraffin-embedded (FFPE) tissue corresponding to Hematoxylin and Eosin (HE)-stained slides was used to ensure that at least 20% of the retrieved cells were neoplastic. Genomic DNA was extracted from FFPE tissues by Qiagen AllPrep DNA/RNA Kit. The isolated genomic DNA was subject to targeted sequencing by using Illumina TruSeq Amplicon Cancer Panel which includes highly cancerassociated 48 genes. Results: The most common mutation was APC (3/5 cases), ATM (3/5 cases), ErbB family mutations (3/5 cases). The angiogenesis pathway including the genes EGFR and FGFR are seen in 2/5 cases. PTPN11 gene was also found in 2/5 cases. However VHL mutation was not found in any of the cases. However, CAIX was expressed diffuse and strongly in all 5 cases of hemangioblastoma. Therefore, expression of CAIX in absence of VHL mutation raises possibility of alternate interactions of downstream proteins, HIFa and CAIX, EGFR and FGFR. Conclusions: In this study, we demonstrated multiple genes that are mutated in hemangioblastoma, especially, APC, ATM and ErbB family mutations are highly associated with this tumor. Notably, VHL mutation was not detected among the cases, may indicate VHL structure variant and/or epigenetic changes. Our data demonstrate clearly difference between clear cell renal cell carcinoma and hemangioblastomas at molecular level.