Asian Pacific Journal of Cancer Prevention

  • 제16권5호
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  • Pages.1977-1980
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  • 2015
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  • 1513-7368(pISSN)
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  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
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VHL Gene Mutation Analysis of a Chinese Family with Non-Syndromic Pheochromocytomas and Patients with Apparently Sporadic Pheochromocytoma

  • Zhang, Bin (Department of Urology, Lanzhou General Hospital of Lanzhou Command) ;
  • Qian, Jing (Department of Urology, Gansu Provincial People's Hospital) ;
  • Chang, De-Hui (Department of Urology, Lanzhou General Hospital of Lanzhou Command) ;
  • Wang, Yang-Min (Department of Urology, Lanzhou General Hospital of Lanzhou Command) ;
  • Zhou, Da-Hai (Department of Urology, PLA 401 Hospital) ;
  • Qiao, Gou-Mei (Department of Urology, Lanzhou General Hospital of Lanzhou Command)
  • 발행 : 2015.03.18
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초록

Objective: The Von Hippel-Lindau syndrome (VHLD), an inherited neoplastic syndrome predisposing to central nervous system hemangioblastoma (CNS), pheochromocytoma (PCC), renal cell carcinoma(RCC), retinal hemangioma (RA) and renal cysts, is caused by mutations or deletions of the VHL tumor-suppressor gene. To assess VHL genotype-phenotype correlations with function of pVHL a gene mutation analysis of members in a Chinese family with non-syndromic PCCs and individuals with apparently sporadic pheochromocytoma (ASP) was performed. Materials and Methods: DNA samples of 20 members from the Chinese family with non-syndromic PCCs and 41 patients with ASP were analyzed by polymerase chain reaction and direct sequencing, confirmed by Taqman probe. Results: Three novel mutations (H125P, 623(^TTTGTtG) and R120T) were identified in the Chinese family and in 3 among 41 ASP patients. The mutations were all located in exon 2 of VHL gene encoding ${\beta}$-domain of pVHL. The tumor type in H125P carriers and R120T carriers was VHL type 2C. And 623(^TTTGTtG) carriers presented VHL type 2B or type 2C. Conclusions: VHL gene abnormalities were identified in the Chinese family with non-syndromic PCCs and patients with APS, resulting in dysfunction of pVHL. H125P and R120T could be associated with VHL type 2C, while 623(^TTTGTtG) might be linked with VHL type 2B or type 2C. Not only is the genetic analysis helpful for early diagnosis and treatment of patients with VHLD, it is also benefitial for research intoVHLD pathogenesis.

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참고문헌

  1. Ali Tootee, Hasani-Ranjbar S (2012). Von hippel-lindau disease: a new approach to an old problem. Int J Endocrinol Metab, 4, 619-24.
  2. Andreasson A, Kiss NB, Caramuta S, et al (2013). The VHL gene is epigenetically inactivated in pheochromocytomas and abdominal paragangliomas. Epigenetics, 12, 1347-54.
  3. Bausch B, Wellner U, Bausch D, et al (2013). Long-term prognosis of patients with pediatric pheochromocytoma. Endocr Relat Cancer, 1, 17-25.
  4. Binderup ML, Bisgaard ML, Harbud V, et al (2013). Von hippellindau disease (VHL). Dan Med J, 12, 4763.
  5. Chen J, Geng W, Zhao Y, Zhao H, et al (2013). Clinical and mutation analysis of four Chinese families with von Hippel- Lindau disease. Clin Transl Oncol, 5, 391-7.
  6. GAO Yong, HUANG Yan-ping, TU Xiang-an, et al (2013). Genetic characterization and protein stability analysis of a Chinese family with von hippel-lindau disease. Chin Med J, 19, 3690-93.
  7. Jime'nez C, Cote G, Arnold A,et al (2006). Review: should patients with apparently sporadic pheochromoeytomas or paragangliomas be screened for hereditary syndromes. J Chn Endocrinol Metab, 8, 2851-58.
  8. Kim J, Seong MW, Lee K, et al (2013). Germline mutations and genotype-phenotype correlations in patients with apparently sporadic pheochromocytoma/paraganglioma in Korea. Clin Genet, 5, 482-6.
  9. King KS, Pacak K (2013). Familial pheochromocytomas and paragangliomas. Mol Cell Endocrinol, 1-2, 92-100.
  10. Lanikova L, Lorenzo F, Yang C, et al (2013). Novel homozygous VHL mutation in exon 2 is associated with congenital polycythemia but not with cancer. Blood, 19, 3918-24.
  11. Lon ser RR, G lenn GM, W altherM, et al (2003). von-Hippel Lindau disease. Lancet, 9374, 2059-67.
  12. Mete T, Berker D, Yilmaz E, et al (2013). Clinical presentation of Von Hippel Lindau syndrome type 2B associated with VHL. Endocrine, 1, 128-35.
  13. Qi XP, Liu WT, Li JY, et al (2013). p.N78S and p.R161Q germline mutations of the VHL gene are present in von Hippel-Lindau syndrome in two pedigrees. Mol Med Rep, 3, 799-805.
  14. Vaganovs P, Bokums K, Miklasevics E, et al (2013). Von hippel-lindau syndrome: diagnosis and management of hemangioblastoma and pheochromocytoma. Case Rep Urol, 2013, 624096.
  15. Zhang B, Wang YM, Wang N, Ha XQ, et al (2009). Genetic detection and analysis of the VHL gene in patients with sporadic pheochromocytoma. Chin J Oncol, 5, 361-5.
  16. Zhou DH, Wang YM, Lan T, et al (2007). Mutation screening of VHL gene in a Chinese family with non-syndromic pheochromocytoma. Chin J Med Genet, 4, 365-68.
  17. Zinnamosca L, Laudisi A, Petramala L, et al (2013). Von Hippel Lindau disease with colon adenocarcinoma, renal cell carcinoma and adrenal pheochromocytoma. Intern Med, 14, 1599-603.