ASXL3

Overview

ASXL3 (ASXL transcriptional regulator 3) is a chromatin-associated protein involved in polycomb-mediated gene regulation. In neuroblastoma, it is a marker of the high-risk undifferentiated tumor cluster that shares a transcriptional program with a postnatal human adrenal progenitor population.

Alterations observed in the corpus

  • ASXL3 is part of the progenitor/migratory gene program shared between the normal postnatal human adrenal progenitor cluster (hC1) and the undifferentiated high-risk neuroblastoma cluster (nC3), alongside BCL11A, ERBB3, RTTN, TP63, POU6F2, SOX6, CLDN11, and DOCK7; identified by single-nuclei RNA-seq of 11 neuroblastoma tumors PMID:34493726.

Cancer types (linked)

  • Neuroblastoma (NBL) — ASXL3 marks the high-risk undifferentiated nC3 cluster enriched for MYCN-amplified and/or 11q-deleted tumors; its shared expression with the postnatal hC1 progenitor supports the hypothesis that high-risk NBL may arise from a postnatal TRKB+ cholinergic progenitor PMID:34493726.

Co-occurrence and mutual exclusivity

  • Co-expressed with BCL11A, CLDN11, NTRK2, and CHRNA7 in the hC1/nC3 shared progenitor program; mutually exclusive with the noradrenergic/NTRK1-high low-risk tumor clusters PMID:34493726.

Therapeutic relevance

  • Not directly therapeutically targeted in the corpus; identified as a potential marker of the cell-of-origin for high-risk neuroblastoma PMID:34493726.

Open questions

  • Whether ASXL3 loss-of-function contributes to the undifferentiated phenotype of high-risk neuroblastoma, as has been reported in other developmental contexts, is not addressed in the corpus.

Sources

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