ARHGAP26

Overview

ARHGAP26 (Rho GTPase-activating protein 26, also known as GRAF) is a RhoGAP-domain protein that regulates RHO-family GTPase activity. In gastric cancer, in-frame fusions of CLDN18 with ARHGAP26 or ARHGAP6 are a defining genomic feature of the genomically stable (GS) subtype.

Alterations observed in the corpus

• CLDN18-ARHGAP26 in-frame fusion from t(3;5) and related rearrangements present in 15% of GS gastric tumours; mutually exclusive with RHOA mutation; the chimaeric protein arises via cryptic splice activation downstream of the CLDN18 exon 5 stop codon PMID:25079317

Cancer types (linked)

• STAD: CLDN18-ARHGAP26 fusion in ~15% of GS subtype tumours; mutually exclusive with RHOA hotspot mutations; proposed as a RHO-signaling and cell-adhesion driver PMID:25079317

Co-occurrence and mutual exclusivity

• Mutually exclusive with RHOA mutation in GS gastric tumours PMID:25079317

Therapeutic relevance

• GS subtype with CLDN18-ARHGAP fusions points to RHO-pathway modulation and cell-adhesion biology as candidate therapeutic targets PMID:25079317

Open questions

• Functional consequences of the CLDN18-ARHGAP26 fusion for ARHGAP/RHO regulation and CLDN18 adhesion are inferred but not biochemically confirmed PMID:25079317

Sources

• PMID:25079317

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