Ricerc@Sapienza

Background: The diagnosis of diffuse intrinsic pontine glioma (DIPG) is based largely on a combination of clinical and radiological findings due to the difficulty of obtaining a biopsy. An accurate evaluation of magnetic resonance imaging (MRI) scans is consequently essential. Recent analyses on the genomic landscape of DIPG revealed recurrent mutations in the H3F3A and HIST1H3B histone genes. We reviewed cases with available tumor tissue from institutional DIPG series to ascertain the consistency between their histo-molecular findings and clinical-radiological features. Methods: We conducted a radiological and pathological review of 22 cases of DIPG. We performed immunohistochemical analyses to detect H3F3A/HIST1H3B K27M mutations, histone tri-methylation and EZH2 expression. Mutational analysis was performed for ACVR1, H3F3A and HIST1H3B genes. Results: Patients’ median age at diagnosis was 8 years, and their median overall survival was 11 months. Nineteen/22 cases (86%) showed evidence of K27M mutation on immunohistochemistry and/or mutation analysis. Histone tri-methylation expression was low or lacking in these mutated cases. Sequence analysis revealed 13 cases with H3F3A and one case with HIST1H3B K27M mutation. There was no significant difference in EZH2 expression between the K27M-mutant and wild-type DIPGs. On external, blinded MRI re-evaluation, all but one lesion were consistent with DIPG; the one lesion that was not showed no evidence of K27M mutation and retained histone trimethylation expression. Conclusion: In conclusion, our study demonstrates a high frequency of histone K27M mutations in DIPG when MRI features are carefully assessed, thus confirming the consistency of imaging with biological markers in our institutional series of DIPG.