PHOX2A
Overview
PHOX2A (Paired-Like Homeobox 2A) is a homeodomain transcription factor essential for the development of noradrenergic neurons and the autonomic nervous system. In neuroblastoma, PHOX2A is a defining marker of the noradrenergic (NOR) tumor subpopulation associated with low-risk disease and favorable prognosis.
Alterations observed in the corpus
- PHOX2A is significantly over-expressed in noradrenergic (NOR) tumor clusters (nC5/nC7/nC8/nC9) of neuroblastoma relative to undifferentiated nC3 cells (FDR <0.01, Welch’s t-test) in a single-nuclei RNA-seq study of 11 tumors (Smart-Seq2). Co-expressed with PHOX2B, TH, DBH, and ISL1 as part of the noradrenergic/adrenergic panel. PMID:34493726
Cancer types (linked)
- NBL — marker of NOR tumor clusters enriched in low-risk neuroblastoma; NOR cluster signatures (nC7/nC8) associate with better overall survival in the 498-sample SEQC cohort (Kaplan-Meier, Bonferroni-corrected P <0.01). PHOX2A marks postnatal chromaffin cells in normal adrenal gland as well. PMID:34493726
Co-occurrence and mutual exclusivity
Therapeutic relevance
- PHOX2A expression marks favorable-prognosis NOR neuroblastoma cells; no direct targeted therapy is reported in the corpus.
Open questions
- Whether enforced PHOX2A expression can drive differentiation of undifferentiated nC3 cells toward the NOR fate is not addressed in the corpus. PMID:34493726
Sources
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