NACC2

Overview

NACC2 (Nucleus Accumbens Associated 2) encodes a transcriptional repressor containing a BEN domain. In cancer genomics, NACC2 has been identified as a 5’ fusion partner for NTRK2 in pediatric brain tumors, contributing a dimerization domain predicted to confer ligand-independent kinase activation.

Alterations observed in the corpus

  • Identified as a novel 5’ fusion partner for NTRK2 in pilocytic astrocytoma; the NACC2:NTRK2 fusion retains the NTRK2 kinase domain and the NACC2 BEN domain contributes dimerization predicted to drive ligand-independent activation (3 non-cerebellar samples total across QKI:NTRK2 and NACC2:NTRK2 fusions) PMID:23817572

Cancer types (linked)

  • Pilocytic astrocytoma: fusion partner in NTRK2-activating gene fusions PMID:23817572

Co-occurrence and mutual exclusivity

  • NACC2:NTRK2 fusion occurs in non-cerebellar pilocytic astrocytomas lacking KIAA1549:BRAF fusions; QKI is the other novel 5’ partner for NTRK2 in the same series PMID:23817572

Therapeutic relevance

  • The NACC2:NTRK2 fusion nominates NTRK2 (TrkB) inhibition as a therapeutic strategy in non-cerebellar pilocytic astrocytomas where surgical resection is limited PMID:23817572

Open questions

  • Whether NACC2:NTRK2 fusions respond to TRK inhibitors (e.g., larotrectinib, entrectinib) has not been directly tested in this tumor context.

Sources

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