Alterations in the RB Pathway With Inactivation of RB1 Characterize Glioblastomas With a Primitive Neuronal Component

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Abstract

A primitive neuronal component is a feature of some glioblastomas but defining molecular alterations of this histologic variant remains uncertain. We performed next-generation sequencing of 1500 tumor related genes on tissue from 9 patients with glioblastoma with a primitive component (G/PN) and analyzed 27 similar cases from the Cancer Genome Atlas (TCGA) dataset. Alterations in the RB pathway were identified in all of our patients' tumors and 81% of TCGA tumors with the retinoblastoma tumor suppressor gene (RB1) commonly affected. Although RB1 mutations were observed in some conventional glioblastomas, the allelic fractions of these mutations were significantly higher in tumors with a primitive neuronal component in both our and TCGA cohorts (median, 72% vs 25%, p < 0.001 and 80% vs 40%, p < 0.02, respectively). Further, in 78% of patients in our cohort, RB expression was lost by immunohistochemistry. Our findings indicate that alterations in the RB pathway are common in G/PNs and suggest that inactivation of RB1 may be a driving mechanism for the phenotype.

Original languageEnglish (US)
Pages (from-to)1092-1098
Number of pages7
JournalJournal of neuropathology and experimental neurology
Volume80
Issue number12
DOIs
StatePublished - Dec 29 2021

Keywords

  • Glioblastoma
  • Primitive neuronal tumor
  • RB1
  • Retinoblastoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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