Abstract Introduction T; small fragment deletion/insertion: c. 224-6delTCT; nonsense mutation: c. 481CT; splicing mutation: c. 463+1GA; and large fragment deletion: exon 2 deletion. Cerebellar hemangioblastoma was the most prevalent clinical manifestation in patients with VHL syndrome (61. 0%), followed by renal cell carcinoma (53. 5%). Additionally, 61. 3% of patients exhibited two or more concurrent conditions. Further analysis of high-frequency mutations and their association with renal cell carcinoma showed that missense mutation c. 486CG (71. 4%), large fragment deletion of exon 3 (75. 0%), and nonsense mutation c. 481CT (70. 0%) were linked to a higher incidence of renal cell carcinoma. Logistic regression analysis revealed that large fragment deletion of exon 3 was associated with a higher risk of renal cell carcinoma compared to other mutation types (OR: 2. 866, 95% CI: 1. 070–7. 677, P=0. 031). Conclusions The type and location of high-frequency mutations in the VHL gene are closely correlated with specific phenotypic manifestations. Future genotype-phenotype studies should focus on the functional domains of the VHL gene, and further investigation into the molecular mechanisms underlying these genotype-phenotype correlations is needed. Citation Format: Chuandong Wang, Kan Gong. Common VHL mutations and the genotype-phenotype correlation: A retrospective study of 1172 patients with von Hippel-Lindau syndrome in China abstract. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Kidney Cancer Research: From Molecular Insights to Therapeutic Breakthroughs; 2026 Mar 13-16; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86 (5Suppl₂): Abstract nr B011.
Wang et al. (Fri,) studied this question.