Supplementary Methods

Literature search, TCGA and institution cases

A systematic search of published data sets was performed using PubMed and Google Scholar from 2012 to November, 2017. Search terms included: “K27M”, “histone H3”, and “H3F3A K27M”. No initial restrictions were made with regards to study design, sample size, publication date, or availability of clinical data (i.e., all studies with K27M/I-mutant cases were initially included). Sources included published studies, abstracts, and data repositories[3-18]. Factors extracted included age, sex, overall survival, survival status, tumor location and laterality, histopathologic diagnosis, WHO grade, and growth pattern (diffuse or non-diffuse/circumscribed) (see Online Resource 2 for list of abbreviations). Mutation data included: gene (H3F3A [H3.3], HIST1H3B [H3.1], HIST1H3C [H3.1], HIST2H3C [H3.2]), point mutation (K27M, K27I, G34R/V, H3-wildtype), and co-occurring somatic mutations (IDH, ATRX, P53). When discrepancies existed in clinical details between studies, the individual samples were excluded from final analysis.When reported, IDH-mutant gliomas, determined either by IHC or PCR, were excluded from the study. H3-wildtype and H3K27M cases from The Cancer Genome Atlas (TCGA) ( were obtained through the cBioPortal and PedcBioPortal for Cancer Genomics[1, 2]. Patient cases were also acquired through collaboration with the Mayo Clinic in Rochester, Minnesota. A small number of cases were included as part of routine consultation and in-house services at the University of Michigan in Ann Arbor, Michigan.

Data extraction

The endpoint extracted from all data sources was overall survival (OS), or time until last follow-up. In cases from institutions with accessible clinical information, overall survival was further specified as the time from radiologic detection until the date of death.Survival times were expressed in months.

Supplemental references

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3Gessi M, Capper D, Sahm F, Huang K, von Deimling A, Tippelt S, Fleischhack G, Scherbaum D, Alfer J, Juhnke BOet al (2016) Evidence of H3 K27M mutations in posterior fossa ependymomas. Acta Neuropathol 132: 635-637 Doi 10.1007/s00401-016-1608-3

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