Pathogenicity of germline VHL variants is associated with renal cell carcinoma size in von Hippel-Lindau disease

• Published in: Archives of Endocrinology and Metabolism Vol. 69; no. 1; pp. 1 - 6
• Main Authors: Mori, Gustavo H., Fagundes, Gustavo F. C., Santana, Lucas S., Freitas-Castro, Felipe, Afonso, Ana Caroline F., Lourenço Jr, Delmar M., Pereira, Maria Adelaide A., Tanno, Fabio Y., Srougi, Victor, Chambo, Jose L., Cordeiro, Mauricio D., Nahas, William C., Hoff, Ana O., Fragoso, Maria Candida B. V., Mendonca, Berenice B., Latronico, Ana Claudia, Almeida, Madson Q.
• Format: Journal Article
• Language: English
• Published: Brazil Brazilian Society of Endocrinology and Metabolism (SBEM) 01.01.2025; Brazilian Society of Endocrinology and Metabolism
• Subjects: Adrenal Gland Neoplasms - genetics; Adrenal Gland Neoplasms - pathology; adrenal paraganglioma; Adult; Aged; Brief Report; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; Female; Genetic Association Studies; genetics; Germ-Line Mutation; Humans; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Male; Middle Aged; Mutation, Missense; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Paraganglioma - genetics; Paraganglioma - pathology; renal cell carcinoma; Retrospective Studies; Von Hippel-Lindau disease; von Hippel-Lindau Disease - complications; von Hippel-Lindau Disease - genetics; von Hippel-Lindau Disease - pathology; Von Hippel-Lindau Tumor Suppressor Protein - genetics; renal cell carcinoma; genetics; adrenal paraganglioma; Von Hippel-Lindau disease
• ISSN: 2359-3997; 2359-4292
• DOI: 10.20945/2359-4292-2024-0354

In this study, our aim was to search for new genotype-phenotype correlations in patients with Von Hippel-Lindau (VHL) disease. We retrospectively studied 53 consecutive patients with VHL disease and confirmed genetic diagnoses from 32 relatives. Most VHL pathogenic or likely pathogenic variants were missense (18 out of 32; 56.25%). The median size of the large carcinoma (RCC) was 3.6 cm (interquartile range, 2.8 to 6.5 cm). Interestingly, the size of the large RCC in patients harboring VHL pathogenic variants (n = 9) was significantly greater than that in patients with VHL likely pathogenic (n = 7) variants (5.4 cm [3.65 to 6.6] vs. 2.9 cm [2.45 to 3.35]; p = 0.008). Moreover, adrenal paraganglioma (PGL) (82.35% vs. 17.65%; p = 0.0001) and pancreatic neuroendocrine tumor (PNET) (81.81% vs. 18.18%; p = 0.007) were associated with missense VHL pathogenic or likely pathogenic variants compared with non-missense defects. In contrast, central nervous system (CNS) hemangioblastomas (HBs) (90.47% vs. 53.12%; p = 0.004), pancreatic cysts (76.19% vs. 28.12%; p = 0.001) and RCCs (57.14% vs. 12.5; p = 0.001) were more common in patients with non-missense VHL variants. VHL pathogenic variants were associated with larger RCCs than were VHL likely pathogenic variants.