ASCL1

Overview

ASCL1 (achaete-scute family bHLH transcription factor 1; also known as MASH1) is a proneural transcription factor required for neuronal and oligodendrocyte differentiation during normal brain development. In oligodendroglioma it is a component of the stem/progenitor transcriptional program, co-expressed with other neural progenitor regulators.

Alterations observed in the corpus

  • ASCL1 is part of the stem/progenitor transcriptional program in grade II IDH-mutant 1p/19q-codeleted oligodendroglioma, co-expressed with SOX2, SOX4, SOX11, NFIB, CHD7, CD24, BOC, TCF4, and CCND2; identified from scRNA-seq of 4,347 cells across 6 tumors PMID:27806376.
  • Neuroendocrine transcription factor and expression marker defining the ASCL1-high SCLC transcriptional subtype; downregulated upon NOTCH activation in mouse models, reflecting inverse relationship between neuroendocrine differentiation and Notch signaling PMID:26168399
  • ASCL1 overexpression with 22q11.21 LOH including SMARCB1 — diagnostic of atypical teratoid/rhabdoid tumor (ATRT) and prognostic for improved outcome in a pediatric pan-cancer sequencing cohort PMID:28007021

Cancer types (linked)

  • ODG — ASCL1 marks the proliferative stem/progenitor apex of oligodendroglioma; this compartment is enriched for cycling cells (MKI67+) and most closely resembles a tri-potent neural progenitor rather than an OPC PMID:27806376.

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • The stem/progenitor program (including ASCL1) defines the small cycling sub-population considered the most plausible therapeutic target in oligodendroglioma; differentiated cells are largely non-cycling and unlikely to fuel long-term tumor growth PMID:27806376.

Open questions

  • Whether ASCL1 activity is required for maintenance of the oligodendroglioma stem/progenitor state or is merely co-expressed is not functionally tested in the corpus.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:26168399

This page was processed by crosslinker on 2026-05-14. - PMID:28007021

This page was processed by entity-page-writer on 2026-05-15.