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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Brazilian Society of Endocrinology and Metabolism
2025-02-01
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| Series: | Archives of Endocrinology and Metabolism |
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| author | 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 |
| author_facet | 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 |
| author_sort | Gustavo H. Mori |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8ca57c0bfd6a4e0181cdf2f3cd79f387 |
| institution | Kabale University |
| issn | 2359-4292 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Brazilian Society of Endocrinology and Metabolism |
| record_format | Article |
| series | Archives of Endocrinology and Metabolism |
| spelling | doaj-art-8ca57c0bfd6a4e0181cdf2f3cd79f3872025-02-11T07:44:16ZengBrazilian Society of Endocrinology and MetabolismArchives of Endocrinology and Metabolism2359-42922025-02-0169110.20945/2359-4292-2024-0354Pathogenicity of germline VHL variants is associated with renal cell carcinoma size in von Hippel-Lindau diseaseGustavo H. Morihttps://orcid.org/0000-0003-3547-6781Gustavo F. C. Fagundeshttps://orcid.org/0000-0003-4097-3029Lucas S. Santanahttps://orcid.org/0000-0003-0428-2386Felipe Freitas-Castrohttps://orcid.org/0000-0002-5340-432XAna Caroline F. Afonsohttps://orcid.org/0009-0002-6179-0854Delmar M. Lourenço Jr.https://orcid.org/0000-0003-1147-4159Maria Adelaide A. Pereirahttps://orcid.org/0000-0002-9576-1587Fabio Y. Tannohttps://orcid.org/0000-0001-9148-8002Victor Srougihttps://orcid.org/0000-0001-8346-3833Jose L. Chambohttps://orcid.org/0009-0006-3686-5892Mauricio D. Cordeirohttps://orcid.org/0000-0001-8439-3283William C. Nahashttps://orcid.org/0000-0002-7395-8370Ana O. Hoffhttps://orcid.org/0000-0002-7058-6321Maria Candida B. V. Fragosohttps://orcid.org/0000-0001-6150-1915Berenice B. Mendoncahttps://orcid.org/0000-0003-1762-1084Ana Claudia Latronicohttps://orcid.org/0000-0001-6782-693XMadson Q. Almeidahttps://orcid.org/0000-0002-2957-6148ABSTRACT 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972025000101500&lng=en&tlng=enVon Hippel-Lindau diseaserenal cell carcinomaadrenal paragangliomagenetics |
| spellingShingle | 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 Pathogenicity of germline VHL variants is associated with renal cell carcinoma size in von Hippel-Lindau disease Archives of Endocrinology and Metabolism Von Hippel-Lindau disease renal cell carcinoma adrenal paraganglioma genetics |
| title | Pathogenicity of germline VHL variants is associated with renal cell carcinoma size in von Hippel-Lindau disease |
| title_full | Pathogenicity of germline VHL variants is associated with renal cell carcinoma size in von Hippel-Lindau disease |
| title_fullStr | Pathogenicity of germline VHL variants is associated with renal cell carcinoma size in von Hippel-Lindau disease |
| title_full_unstemmed | Pathogenicity of germline VHL variants is associated with renal cell carcinoma size in von Hippel-Lindau disease |
| title_short | Pathogenicity of germline VHL variants is associated with renal cell carcinoma size in von Hippel-Lindau disease |
| title_sort | pathogenicity of germline vhl variants is associated with renal cell carcinoma size in von hippel lindau disease |
| topic | Von Hippel-Lindau disease renal cell carcinoma adrenal paraganglioma genetics |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972025000101500&lng=en&tlng=en |
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