MAGI2

Overview

MAGI2 (Membrane-Associated Guanylate Kinase Inverted 2) encodes a scaffolding protein that binds and stabilizes PTEN, thereby promoting PTEN-mediated suppression of PI3K/AKT signaling. Recurrent structural rearrangements in MAGI2 in melanoma effectively mimic PTEN loss, implicating it as an indirect tumor suppressor in PI3K pathway regulation.

Alterations observed in the corpus

  • MAGI2 is recurrently rearranged in 3/25 metastatic melanomas (WGS discovery cohort); disruption of MAGI2 destabilizes PTEN and is functionally equivalent to PTEN loss PMID:22622578
  • Recurrent disruptive rearrangements identified in prostate adenocarcinoma via chromoplexy, alongside GSK3B and FOXO1, implicating MAGI2 in prostate cancer signaling; functional consequences not experimentally validated PMID:23622249

Cancer types (linked)

  • SKCM (Melanoma): Structural rearrangements in 3/25 discovery WGS tumors; co-occurs with PTEN rearrangements across the cohort PMID:22622578

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • MAGI2 loss activates the PI3K/AKT pathway; patients with MAGI2 rearrangements may show functional equivalence to PTEN-null tumors, with potential sensitivity to PI3K or AKT inhibitors, though no direct clinical data are available.

Open questions

  • Whether MAGI2 rearrangements are mutually exclusive with direct PTEN mutations or co-occur, and whether combined loss confers additive pathway activation, is not resolved in the current corpus.

Sources

This page was processed by crosslinker on 2026-05-09. - PMID:23622249

This page was processed by crosslinker on 2026-05-09.