A germline variant of ring finger protein 43 in an early onset, treatment-resistant metastatic gastric cancer: a case report.

Abstract

Background: Ring finger protein 43 (RNF43) is an E3 ubiquitin-protein ligase that functions as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination, endocytosis, and subsequent degradation of Frizzled receptors within the Wnt receptor complex. It exerts its effects on both canonical and non-canonical Wnt signaling pathways.

Case description: This case report describes a 49-year-old female patient with a significant family history of cancer and parental consanguinity who was diagnosed with treatment-resistant stage IV gastric adenocarcinoma. Genomic profiling conducted via liquid biopsy identified a missense variant in RNF43 exon 9 (NM_017763.6, c.1948C>T; Arg650Ter) with a high variant allele frequency (VAF) of 49.5%. Confirmation of the R650* variant at the germline level underscores its clinical significance in early onset gastric cancer (GC) pathogenesis.

Conclusions: While interpretations of its pathogenicity vary in the ClinVar database, the application of the American College of Medical Genetics (ACMG) criteria suggests its potential involvement in cancer pathogenesis. This report highlights the necessity for further research to elucidate the role and impact of RNF43 in GC progression and develop specific preventive measures for affected families as genetic testing and counseling in high-risk families.