Genomic analysis of dysembryoplastic neuroepithelial tumor spectrum reveals a diversity of molecular alterations dysregulating the MAPK and PI3K/mTOR pathways

Lea F. Surrey*, Payal Jain, Bo Zhang, Joshua Straka, Xiaonan Zhao, Brian N. Harding, Adam C. Resnick, Phillip B. Storm, Anna Maria Buccoliero, Lorenzo Genitori, Marilyn M. Li, Angela J. Waanders, Mariarita Santi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Dysembryoplastic neuroepithelial tumors (DNT) lacking key diagnostic criteria are challenging to diagnose and sometimes fall into the broader category of mixed neuronal-glial tumors (MNGT) or the recently described polymorphous low-grade neuroepithelial tumor of the young (PLNTY). We examined 41 patients with DNT, MNGT, or PLNTY for histologic features, genomic findings, and progression-free survival (PFS). Genomic analysis included sequence and copy number variants and RNA-sequencing. Classic DNT (n ¼ 26) was compared with those with diffuse growth without cortical nodules (n ¼ 15), 6 of which exhibited impressive CD34 staining classifying them as PLNTY. Genomic analysis was complete in 33, with sequence alterations recurrently identified in BRAF, FGFR1, NF1, and PDGFRA, as well as 7 fusion genes involving FGFR2, FGFR1, NTRK2, and BRAF. Genetic alterations did not distinguish between MNGTs, DNTs, or PLNTYs; however, FGFR1 alterations were confined to DNT, and PLNTYs contained BRAF V600E or FGFR2 fusion genes. Analysis of PFS showed no significant difference by histology or genetic alteration; however, numbers were small and follow-up time short. Further molecular characterization of a PLNTY-related gene fusion, FGFR2-CTNNA3, demonstrated oncogenic potential via MAPK/PI3K/mTOR pathway activation. Overall, DNT-MNGT spectrum tumors exhibit diverse genomic alterations, with more than half (19/33) leading to MAPK/PI3K pathway alterations.

Original languageEnglish (US)
Pages (from-to)1100-1111
Number of pages12
JournalJournal of neuropathology and experimental neurology
Volume78
Issue number12
DOIs
StatePublished - Dec 1 2019

Keywords

  • Dysembryoplastic neuroepithelial tumors (DNT)
  • MAP kinase pathway
  • Next generation sequencing
  • Polymorphous low-grade neuroepithelial tumor of the young (PLNTY)

ASJC Scopus subject areas

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

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