García-Bloj Benjamín, Celis Santiago Farah, Orellana Natalia Eva, de Mayo Glasser Tomás, Sáez Mauricio A, Retamal Ignacio N, Muñoz-Medel Matías, Sánchez Carolina, Pinto Felipe, Aravena Paola, Martín Cristopher San, Sabioncello H Andrea C, Villanueva Marcelo Garrido, Sigler Chávez Fernando, Ríos Leal Juvenal A, Manque Patricio A, Erpel José M, Godoy Juan A, Garrido Marcelo
Precision Oncology Center, Faculty of Medicine and Health Sciences, Mayor University, Santiago, Chile.
Precision Health Laboratory, Faculty of Health Sciences, Catholic University of Temuco, Temuco, Chile.
J Gastrointest Oncol. 2025 Aug 30;16(4):1749-1755. doi: 10.21037/jgo-2025-77. Epub 2025 Aug 20.
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.
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.
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.
无名指蛋白43（RNF43）是一种E3泛素蛋白连接酶，通过介导Wnt受体复合物中卷曲受体的泛素化、内吞作用及随后的降解，作为Wnt信号通路的负调节因子发挥作用。它对经典和非经典Wnt信号通路均有影响。
本病例报告描述了一名49岁女性患者，有显著的癌症家族史且父母近亲结婚，被诊断为IV期治疗抵抗性胃腺癌。通过液体活检进行的基因组分析在RNF43外显子9中鉴定出一个错义变异（NM_017763.6，c.1948C>T；Arg650Ter），变异等位基因频率（VAF）高达49.5%。种系水平上R650*变异的确认强调了其在早发性胃癌（GC）发病机制中的临床意义。
虽然ClinVar数据库对其致病性的解释各不相同，但应用美国医学遗传学学会（ACMG）标准表明其可能参与癌症发病机制。本报告强调了进一步研究以阐明RNF43在GC进展中的作用和影响的必要性，并为受影响家庭制定特定的预防措施，作为高危家庭的基因检测和咨询。
