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

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

ABSTRACT Objective: In this study, our aim was to search for new genotype-phenotype correlations in patients with Von Hippel-Lindau (VHL) disease. Subjects and methods: We retrospectively studied 53 consecutive patients with VHL disease and confirmed genetic diagnoses from 32 relatives. Results:...

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Main Authors: Gustavo H. Mori, Gustavo F. C. Fagundes, Lucas S. Santana, Felipe Freitas-Castro, Ana Caroline F. Afonso, Delmar M. Lourenço Jr., Maria Adelaide A. Pereira, Fabio Y. Tanno, Victor Srougi, Jose L. Chambo, Mauricio D. Cordeiro, William C. Nahas, Ana O. Hoff, Maria Candida B. V. Fragoso, Berenice B. Mendonca, Ana Claudia Latronico, Madson Q. Almeida
Format: Article
Language:English
Published: Brazilian Society of Endocrinology and Metabolism 2025-02-01
Series:Archives of Endocrinology and Metabolism
Subjects:
Von Hippel-Lindau disease
renal cell carcinoma
adrenal paraganglioma
genetics
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972025000101500&lng=en&tlng=en
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Summary:ABSTRACT Objective: In this study, our aim was to search for new genotype-phenotype correlations in patients with Von Hippel-Lindau (VHL) disease. Subjects and methods: We retrospectively studied 53 consecutive patients with VHL disease and confirmed genetic diagnoses from 32 relatives. Results: 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. Conclusion: VHL pathogenic variants were associated with larger RCCs than were VHL likely pathogenic variants.
ISSN:2359-4292

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