HOXD13

Overview

HOXD13 is a homeobox transcription factor identified as a master regulator of IDH-mutant astrocytoma progression. It is epigenetically activated at recurrence via gain of H3K27ac and H3K4me3 marks, and CRISPR knockout reduces glioma cell proliferation.

Alterations observed in the corpus

  • HOXD13 is epigenetically activated in recurrent IDH-mutant non-codeleted gliomas: increased H3K27ac and H3K4me3 peaks and significantly overexpressed at recurrence (t-test P=0.0019; N=24 paired samples from the GLASS consortium) PMID:38117484.
  • CRISPR knockout of HOXD13 in a patient-derived IDH-wildtype glioma cell line resulted in decreased cell proliferation in a time-dependent manner PMID:38117484.
  • 83 epigenetically regulated genes in IDH-mutant non-codeleted glioma progression were experimentally confirmed as HOXD13 targets, including CENPF, PCNA, and HOXA7 PMID:38117484.

Cancer types (linked)

  • DIFG / ASTR — master epigenetic regulator identified in IDH-mutant astrocytoma progression from the GLASS consortium (132 matched initial and recurrent gliomas); activation associated with GCIMP-high to GCIMP-low transition after treatment PMID:38117484.

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • HOXD13 and its downstream targets (CENPF, PCNA, HOXA7) are candidate therapeutic targets in recurrent IDH-mutant glioma PMID:38117484.

Open questions

  • HOXD13 functional validation was limited to an IDH-wildtype cell line; the biology may differ in the IDH-mutant GCIMP-low context due to the lack of available IDH-mutant recurrent cell lines PMID:38117484.
  • Whether HOXD13 activation is a cause or consequence of DNA hypomethylation during glioma progression requires prospective investigation PMID:38117484.

Sources

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