GNAI1

Overview

GNAI1 encodes a G protein alpha subunit (Gi1) involved in signal transduction. In pilocytic astrocytoma, GNAI1 was identified as a novel 5’ fusion partner for BRAF, contributing to the growing catalogue of BRAF fusion partners that activate the MAPK pathway in this tumor type.

Alterations observed in the corpus

• Identified as a novel 5’ fusion partner for BRAF in pilocytic astrocytoma by whole-genome sequencing (n=96); all BRAF fusions disrupt the leucine-rich negative regulatory domain and produce constitutive BRAF kinase activation PMID:23817572

Cancer types (linked)

• Pilocytic astrocytoma — GNAI1:BRAF fusion identified as one of several novel BRAF fusion partners in tumors lacking the canonical KIAA1549:BRAF fusion PMID:23817572

Co-occurrence and mutual exclusivity

• Alternative 5’ fusion partner for BRAF, alongside KIAA1549 (70/96 cases), FAM131B, RNF130, CLCN6, and MKRN1 PMID:23817572

Therapeutic relevance

• BRAF fusions activate the MAPK pathway; MEK inhibition is a rational strategy for fusion-positive pilocytic astrocytomas; caution advised against non-V600E-selective BRAF inhibitors due to paradoxical MAPK activation risk PMID:23817572

Open questions

• Functional validation of GNAI1:BRAF specifically has not been reported; frequency of this individual fusion is not specified beyond being one of several rare events PMID:23817572

Sources

• PMID:23817572

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