PMID- 8641695
OWN - NLM
STAT- MEDLINE
DCOM- 19960712
LR  - 20190722
IS  - 0340-6717 (Print)
IS  - 0340-6717 (Linking)
VI  - 97
IP  - 6
DP  - 1996 Jun
TI  - Detection of a germline mutation and somatic homozygous loss of the von 
      Hippel-Lindau tumor-suppressor gene in a family with a de novo mutation. A 
      combined genetic study, including cytogenetics, PCR/SSCP, FISH, and CGH.
PG  - 770-6
AB  - von Hippel-Lindau (VHL) disease is a pleiotropic disorder featuring a variety of 
      malignant and benign tumors of the eye, central nervous system, kidney, and 
      adrenal gland. Recently the VHL gene has been identified in the chromosomal 
      region 3p25-26. Prognosis and successful management of VHL patients and their 
      descendants depend on unambiguous diagnosis. Due to recurrent hemangioblastomas, 
      a29-year-old patient without familial history of VHL disease was diagnosed to be 
      at risk for the disease. Histopathological examination of a small renal mass 
      identified a clear cell tumor with a G1 grading. Genetic characterization of the 
      germline and of the renal tumor was performed. Polymerase chain reaction/single 
      strand conformation polymorphism (PCR/SSCP) analysis with primers from the VHL 
      gene identified a deletion of a single nucleotide in exon 2 in the patient's 
      germline and in the tumor, but not in the DNA of his parents. This deletion 
      therefore must be a de novo mutation. Comparative genome hybridization (CGH) and 
      fluorescence in situ hybridization (FISH) analysis of the G1 tumor with 
      differentially labelled yeast artifical chromosome (YAC) clones showed loss of 3p 
      and of the 3p26 signals, respectively. In conclusion, we identified a de novo 
      germline mutation in the VHL gene of a young patient and a somatic chromosome 3p 
      loss at the homologous chromosome 3 in his renal tumor. Our results suggest a 
      recessive mode of inactivation of the VHL gene, providing solid evidence for its 
      tumor-suppressor gene characteristics. Our data show the diagnostic potential of 
      genetic testing, especially in patients without VHL family history. Furthermore, 
      the findings of homozygous inactivation of the VHL gene in a G1 tumor support the 
      notion that the inactivation of the VHL gene is an early event in tumorigenesis 
      of renal cell carcinoma.
FAU - Decker, H J
AU  - Decker HJ
AD  - Department of Haematology and Oncology, Johannes-Gutenberg University of Mainz, 
      Germany.
FAU - Neuhaus, C
AU  - Neuhaus C
FAU - Jauch, A
AU  - Jauch A
FAU - Speicher, M
AU  - Speicher M
FAU - Ried, T
AU  - Ried T
FAU - Bujard, M
AU  - Bujard M
FAU - Brauch, H
AU  - Brauch H
FAU - Storkel, S
AU  - Storkel S
FAU - Stockle, M
AU  - Stockle M
FAU - Seliger, B
AU  - Seliger B
FAU - Huber, C
AU  - Huber C
LA  - eng
SI  - GENBANK/L15409
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Hum Genet
JT  - Human genetics
JID - 7613873
SB  - IM
MH  - Adult
MH  - *Chromosome Deletion
MH  - Chromosomes, Human, Pair 3/genetics
MH  - DNA Mutational Analysis
MH  - Exons/genetics
MH  - Female
MH  - Genes, Tumor Suppressor/*genetics
MH  - Germ-Line Mutation/*genetics
MH  - Hemangioblastoma
MH  - Homozygote
MH  - Humans
MH  - Karyotyping
MH  - Kidney Neoplasms/*genetics/pathology
MH  - Male
MH  - Molecular Sequence Data
MH  - Pedigree
MH  - Polymerase Chain Reaction/methods
MH  - Polymorphism, Single-Stranded Conformational
MH  - Sequence Deletion/genetics
MH  - Spinal Cord Neoplasms
MH  - von Hippel-Lindau Disease/*genetics
EDAT- 1996/06/01 00:00
MHDA- 1996/06/01 00:01
CRDT- 1996/06/01 00:00
PHST- 1996/06/01 00:00 [pubmed]
PHST- 1996/06/01 00:01 [medline]
PHST- 1996/06/01 00:00 [entrez]
AID - 10.1007/BF02346188 [doi]
PST - ppublish
SO  - Hum Genet. 1996 Jun;97(6):770-6. doi: 10.1007/BF02346188.