PMID- 10554035
OWN - NLM
STAT- MEDLINE
DCOM- 19991202
LR  - 20091119
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 21
DP  - 1999 Nov 1
TI  - Constitutional von Hippel-Lindau (VHL) gene deletions detected in VHL families by 
      fluorescence in situ hybridization.
PG  - 5560-4
AB  - von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited cancer 
      syndrome predisposing to a variety of tumor types that include retinal 
      hemangioblastomas, hemangioblastomas of the central nervous system, renal cell 
      carcinomas, pancreatic cysts and tumors, pheochromocytomas, endolymphatic sac 
      tumors, and epididymal cystadenomas [W. M. Linehan et al., J. Am. Med. Assoc., 
      273: 564-570, 1995; E. A. Maher and W. G. Kaelin, Jr., Medicine (Baltimore), 76: 
      381-391, 1997; W. M. Linehan and R. D. Klausner, In: B. Vogelstein and K. Kinzler 
      (eds.), The Genetic Basis of Human Cancer, pp. 455-473, McGraw-Hill, 1998]. The 
      VHL gene was localized to chromosome 3p25-26 and cloned [F. Latif et al., Science 
      (Washington DC), 260: 1317-1320, 1993]. Germline mutations in the VHL gene have 
      been detected in the majority of VHL kindreds. The reported frequency of 
      detection of VHL germline mutations has varied from 39 to 80% (J. M. Whaley et 
      al., Am. J. Hum. Genet., 55: 1092-1102, 1994; Clinical Research Group for Japan, 
      Hum. Mol. Genet., 4: 2233-2237, 1995; F. Chen et al., Hum. Mutat., 5: 66-75, 
      1995; E. R. Maher et al., J. Med. Genet., 33: 328-332, 1996; B. Zbar, Cancer 
      Surv., 25: 219-232, 1995). Recently a quantitative Southern blotting procedure 
      was found to improve this frequency (C. Stolle et al., Hum. Mutat., 12: 417-423, 
      1998). In the present study, we report the use of fluorescence in situ 
      hybridization (FISH) as a method to detect and characterize VHL germline 
      deletions. We reexamined a group of VHL patients shown previously by 
      single-strand conformation and sequencing analysis not to harbor point mutations 
      in the VHL locus. We found constitutional deletions in 29 of 30 VHL patients in 
      this group using cosmid and P1 probes that cover the VHL locus. We then tested 
      six phenotypically normal offspring from four of these VHL families: two were 
      found to carry the deletion and the other four were deletion-free. In addition, 
      germline mosaicism of the VHL gene was identified in one family. In sum, FISH was 
      found to be a simple and reliable method to detect VHL germline deletions and 
      practically useful in cases where other methods of screening have failed to 
      detect a VHL gene abnormality.
FAU - Pack, S D
AU  - Pack SD
AD  - Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland 
      20892, USA.
FAU - Zbar, B
AU  - Zbar B
FAU - Pak, E
AU  - Pak E
FAU - Ault, D O
AU  - Ault DO
FAU - Humphrey, J S
AU  - Humphrey JS
FAU - Pham, T
AU  - Pham T
FAU - Hurley, K
AU  - Hurley K
FAU - Weil, R J
AU  - Weil RJ
FAU - Park, W S
AU  - Park WS
FAU - Kuzmin, I
AU  - Kuzmin I
FAU - Stolle, C
AU  - Stolle C
FAU - Glenn, G
AU  - Glenn G
FAU - Liotta, L A
AU  - Liotta LA
FAU - Lerman, M I
AU  - Lerman MI
FAU - Klausner, R D
AU  - Klausner RD
FAU - Linehan, W M
AU  - Linehan WM
FAU - Zhuang, Z
AU  - Zhuang Z
LA  - eng
GR  - N01-CO-56000/CO/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
SB  - IM
MH  - Chromosomes, Human, Pair 3
MH  - Family Health
MH  - Female
MH  - *Gene Deletion
MH  - Genetic Testing/methods
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Models, Genetic
MH  - Point Mutation
MH  - von Hippel-Lindau Disease/*genetics
EDAT- 1999/12/20 00:00
MHDA- 1999/12/20 00:01
CRDT- 1999/12/20 00:00
PHST- 1999/12/20 00:00 [pubmed]
PHST- 1999/12/20 00:01 [medline]
PHST- 1999/12/20 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Nov 1;59(21):5560-4.