OTX2

Overview

OTX2 (Orthodenticle Homeobox 2) is a homeodomain transcription factor with roles in brain development. In medulloblastoma, OTX2 is recurrently amplified in subgroup-3 and subgroup-4 tumours, which represent the highest-risk molecular subgroups with the worst prognosis. OTX2 amplification co-occurs with MYCN amplification (including events arising through chromothripsis) and is cooperative with deletions at 9q34 (DDX31/TSC1 locus).

Alterations observed in the corpus

  • Amplification in subgroup-3/4 medulloblastoma (PCGP WGS, 37 tumors); cooperative with DDX31/TSC1 deletion at 9q34; co-occurs with MYCN amplification PMID:22722829
  • Recurrently altered in Group 3 (3%) and Group 4 (6%) medulloblastoma in genome-wide analysis of 491 medulloblastomas PMID:28726821

Cancer types (linked)

  • MB (medulloblastoma): Amplification in subgroup-3/4 tumors, which are the most aggressive molecular subgroups; co-occurs with MYCN amplification PMID:22722829

Co-occurrence and mutual exclusivity

  • Co-occurs with MYCN amplification (including chromothripsis-derived) in subgroup-3/4 medulloblastoma; cooperative with DDX31/TSC1 deletion at 9q34 PMID:22722829

Therapeutic relevance

  • OTX2 amplification marks high-risk subgroup-3/4 medulloblastoma; no direct OTX2-targeted therapies are established. EZH2 inhibitors are proposed as a therapeutic approach for this subgroup PMID:22722829

Open questions

  • The mechanistic cooperation between OTX2 amplification and 9q34 (DDX31/TSC1) deletion is not fully characterised.
  • The relationship between OTX2 amplification and MYCN amplification (cooperative driver vs. co-passenger) requires further study.

Sources

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