Molecularly genetic analysis of von Hippel-Lindau associated central nervous system hemangioblastoma.
Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited cancer predisposition syndrome, characterized by development of a variety of neoplasms in multiple organs. Central nervous system hemangioblastoma (CHB) is the most common manifestation of VHL disease. The germline mutations in the VHL tumor suppressor gene are responsible for the inherited cancer predisposition syndrome. To expand the VHL mutation data and to investigate the tumorigenesis of VHL-associated CNS hemangioblastoma, 24 CHB tissue samples and blood samples of 14 patients from 10 Chinese VHL families were collected and subjected to molecular genetic analysis. Six distinctive germline mutations were identified, and the 601 G to C (Val130Phe) mutation is reported for the first time. Somatic mutations analysis of the VHL gene in VHL-associated CHB showed that loss of heterozygosity (LOH) occurred in more than half of the cases. In addition, expression of the ZAC1 tumor suppressor gene protein was studied using immunohistochemistry staining in CHB tissues with a specific polyclonal antibody. The ZAC1 protein was lost in all CHB. Our data exhibited high frequency of LOH of ZAC1 gene in VHL-associated CHB, indicating that ZAC1 may have a role in tumorigenesis of VHL-associated CHB.
Department of Pathology, Nanjing Jinling Hospital, Clinical School of Medical College of Nanjing University, Nanjing, Jiangsu, China.
Jing
J
Zhou
Jiandong
J
Wang
Nanyun
N
Li
Xinhua
X
Zhang
Hangbo
H
Zhou
Rusong
R
Zhang
Henghui
H
Ma
Xiaojun
X
Zhou
D000293:Adolescent; D000328:Adult; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D018325:Hemangioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D017354:Point Mutation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D006623:von Hippel-Lindau Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D018797:Cell Cycle Proteins; C106464:PLAGL1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human