GENE-42. MOLECULAR AND HISTOLOGIC FEATURES OF A SERIES OF SPORADIC AND FAMILIAL SCHWANNOMAS

Schwannomas are found either sporadically or as part of a syndrome. Genetic alterations found in schwannomas include those in NF2 and SMARCB1 (implicated in schwannomatosis), and BRAF V600E. Reduced copy number of chromosome 22q can be the mechanism for loss of the unaltered allele ofNF2 and/orSMARCB1in some schwannomas. We analyzed a cohort of 57 vestibular and non-vestibular schwannomas from three clinical subtypes (Neurofibromatosis 2, schwannomatosis, and sporadic) for reduced copy number (NF2 and SMARCB1), and mutations (NF2, SMARCB1, LZTR1, NF1 and BRAF). Tumors were histologically classified as conventional/classic, or hybrid. Genomic DNA was extracted from FFPE biopsies. Full coding regions of genes NF1, NF2, LZTR1, SMARCB1 and BRAF were enriched by anchored multiplex-PCR (AMP). Resulting libraries were quantitated and sequenced on the Illumina MiSeq System. Bioinformatics analyses were performed using custom scripts. Copy number alteration was detected using a read depth approach after consolidation of single molecule derived reads. INI1 immunohistochemistry was performed. RNA ISH for SMARCB1 was performed. Five tumors were of hybrid histology, and all five were syndromic. Reduced copy number for NF2 was identified in 33% of vestibular schwannomas and 18% of non-vestibular schwannomas. There was no significant difference in reduced copy number of NF2 between sporadic and syndromic forms. BRAF V600E and NF1 mutations were not identified in any case. For most INI1 mosaics, there was no molecular event explaining the partial loss of INI1 IHC. This study confirms the association of hybrid histology with syndromic schwannomas. NF1 mutations did not explain hybrid histology. We did not find BRAF V600E mutations in this series. INI1 mosaic pattern was not explained by reduced copy number or mutation of SMARCB1 as this was found in only a small number of the cases. These results suggest that loss of INI1 expression could be the result of epigenetic alterations.