CLDN18

Overview

CLDN18 (claudin-18) is a tight-junction protein expressed in the stomach. The CLDN18.2 isoform is a clinically significant therapeutic target in gastric cancer. In the genomically stable (GS) subtype, CLDN18 participates in in-frame chromosomal fusions with ARHGAP26 or ARHGAP6, disrupting cell-adhesion and RHO-pathway regulation.

Alterations observed in the corpus

• CLDN18-ARHGAP26/ARHGAP6 in-frame fusions in 15% of GS gastric tumours; result from t(3;5) and related rearrangements; 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-ARHGAP fusions define a subset of GS tumours (~15%); proposed drivers of RHO-signaling and cell-adhesion dysregulation; GS subtype implicates RHO-pathway modulation as a candidate therapeutic approach PMID:25079317

Co-occurrence and mutual exclusivity

• CLDN18-ARHGAP fusions mutually exclusive with RHOA mutation in GS gastric tumours PMID:25079317

Therapeutic relevance

• CLDN18.2 is a proposed therapeutic target in GS gastric cancer; the fusion event disrupts normal CLDN18 adhesion function PMID:25079317

Open questions

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

Sources

• PMID:25079317

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