Von Hippel-Lindau (VHL) disease is a rare autosomal dominant inherited cancer syndrome that is characterized by hemangioblastomas in the central nervous system and retina, renal cell carcinoma and cysts, pancreatic tumors and cysts, and pheochromocytoma.
The underlying gene in this disease is the VHL tumor suppressor gene. We characterized a family with two affected siblings. The brother and sister displayed VHL type 2B and type 2A features, respectively. Renal lesions in the brother exhibited three different phenotypes, including simple renal cysts, multilocular cystic renal cell carcinoma and clear cell renal cell carcinoma. The phenotypes of the three concurrent renal lesions were first reported in this study. Mutation detection of the VHL gene revealed two recurrent mutations, namely c.256C>T (p.P86S) and c.340+5G>C. The former was predicted to be deleterious and to destabilize the hydrophobic core and lead to VHL dysfunction; however, the latter was predicted to be a benign variant. Our findings provided new data for the genotype-phenotype of VHL diseases and elucidated the pathogenic mechanism with in silico analysis.
Cancer biology & therapy. 2016 Apr 08 [Epub ahead of print]
Ping Yuan, Qipeng Sun, Hao Liang, Wenjun Wang, Ling Li, Ye Wang, Huan Deng, Luhua Lai, Xiaoli Chen, Xiangfu Zhou
a Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation; Department of Obstetrics and Gynecology, IVF Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangzhou, China ., b Department of Urology , Lingnan Hospital, The Third Affiliated Hospital, Sun Yat-sen University , Guangzhou , 510530 , China., c Center for Quantitative Biology, Peking University , Beijing , 100871 , China., a Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation; Department of Obstetrics and Gynecology, IVF Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangzhou, China ., a Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation; Department of Obstetrics and Gynecology, IVF Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangzhou, China ., e Department of Medical Genetics , Zhongshan School of Medicine and Center for Genome Research, Sun Yat-sen University , Guangzhou , 510080 , China., f Department of Pathology , The Third Affiliated Hospital, Sun Yat-sen University , Guangzhou , 510630 , China., c Center for Quantitative Biology, Peking University , Beijing , 100871 , China., a Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation; Department of Obstetrics and Gynecology, IVF Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangzhou, China ., b Department of Urology , Lingnan Hospital, The Third Affiliated Hospital, Sun Yat-sen University , Guangzhou , 510530 , China.