LAUSR

Papillary meningioma (PM) is a World Health Organization (WHO) grade III tumor defined histologically by a perivascular pseudopapillary growth pattern across most of the tumor (> 50%) [10]. A papillary growth pattern in meningiomas has been associated with brain invasion and aggressive clinical behavior [2, 8, 9, 12]. The standard treatment of PM is surgical resection followed by radiation. However, most patients develop recurrences, and metastatic disease is common, particularly to the lung [9, 19]. Another WHO grade III meningioma is the rhabdoid subtype which often harbors mutations in BAP1 [14, 15]. Interestingly, some meningiomas have cells with rhabdoid cytomorphology arranged in a papillary architecture suggesting a potential molecular and genetic link between the papillary and rhabdoid histologic subtypes of meningioma [8, 14]. The genetic alterations associated with PM remain unclear. Major obstacles to molecular characterization include low incidence of tumor, scarcity of tumor tissues available for genomic analyses, and the presence of artifactual pseudo-papillary features in some meningiomas which thereby confound cohorts [2]. To overcome these challenges and identify potentially recurrent somatic alterations in PM subtype of meningiomas, we mined data collected as part of our clinical comprehensive genomic profiling (CGP) initiative which has to date analyzed 8 PM (> 50% papillary morphology) and 22 meningiomas with focal papillary features (10–50%) amongst over 500 additional meningiomas of other subtypes. The samples were analyzed in a CAP/CLIA-accredited laboratory (Foundation Medicine, Cambridge, MA). Approval for this study, including a waiver of informed consent and a HIPAA waiver of authorization, was obtained from the Western Institutional Review Board (Protocol no. 20152817). Three board-certified neuropathologists (E.A.W., S.H.R., and S.S.) confirmed the pathologic diagnosis of each case on routine hematoxylin and eosin-stained slides. DNA was extracted from 40-μm-thick paraffinembedded sections, and CGP was performed on hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of > 650 × for 236 or 315 genes plus the introns from 19 or 28 genes frequently involved in cancer. TMB (tumor mutational burden) was determined on up to Daniel P. Cahill, Shakti H. Ramkissoon, and Tareq A. Juratli contributed equally to this work as co-senior authors.