Acquired ATRX Loss and ALT Phenotype Through Tumor Recurrences in a Case of Pleomorphic Xanthoastrocytoma Suggest Their Possible Roles in Tumor Progression

J Neuropathol Exp Neurol. 2020 Sep 1;79(9):1011-1014. doi: 10.1093/jnen/nlaa074.

Abstract

Pleomorphic xanthoastrocytoma (PXA) is classified as an astrocytic glioma occurring most often in children or young adults. Molecular alterations in PXA are not fully known, especially those associated with tumor progression. We describe a patient with several relapses of a PXA. The tumor showed an acquired ATRX loss through tumor evolution. We tested alternative lengthening of telomeres (ALT) with the C-circle test. While the test was negative in the first tumor, a high circle activity was detected in the last relapse, suggesting an acquired ALT phenotype. Our data not only confirm previous findings of the possible occurrence of ATRX mutations in PXA but also suggest that this alteration is linked to PXA progression. In small biopsies, tumors with ATRX loss, without IDH or histone mutation, pathologists should consider the diagnosis of PXA, especially if associated with BRAF V600E mutation, CDKN2A deletion, and ALT.

Keywords: ATRX; Alternative lengthening of telomeres (ALT); BRAF; Pleomorphic xanthoastrocytoma.

Publication types

  • Case Reports

MeSH terms

  • Astrocytoma / genetics*
  • Astrocytoma / pathology
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Disease Progression
  • Female
  • Humans
  • Mutation
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Phenotype
  • Telomere Homeostasis / genetics*
  • X-linked Nuclear Protein / genetics*
  • Young Adult

Substances

  • ATRX protein, human
  • X-linked Nuclear Protein