PMID- 11284029
OWN - NLM
STAT- MEDLINE
DCOM- 20010614
LR  - 20071115
IS  - 1045-2257 (Print)
IS  - 1045-2257 (Linking)
VI  - 31
IP  - 1
DP  - 2001 May
TI  - Molecular cytogenetic characterization of early and late renal cell carcinomas in 
      von Hippel-Lindau disease.
PG  - 1-9
AB  - Deletions of 3p25, gains of chromosomes 7 and 10, and isochromosome 17q are known 
      cytogenetic aberrations in sporadic renal cell carcinoma (RCC). In addition, a 
      majority of RCCs have loss of heterozygosity (LOH) of the Von Hippel-Lindau (VHL) 
      gene located at chromosome band 3p25. Patients who inherit a germline mutation of 
      the VHL gene can develop multifocal RCCs and other solid tumors, including 
      malignancies of the pancreas, adrenal medulla, and brain. VHL tumors follow the 
      two-hit model of tumorigenesis, as LOH of VHL, a classic tumor suppressor gene, 
      is the critical event in the development of the neoplastic phenotype. In an 
      attempt to define the cytogenetic aberrations from early tumors to late RCC 
      further, we applied spectral karyotyping (SKY) to 23 renal tumors harvested from 
      6 unrelated VHL patients undergoing surgery. Cysts and low-grade solid lesions 
      were near-diploid and contained 1-2 reciprocal translocations, dicentric 
      chromosomes, and/or isochromosomes. A variety of sole numerical aberrations 
      included gains of chromosomes 1, 2, 4, 7, 10, 13, 21, and the X chromosome, 
      although no tumors had sole numerical losses. Three patients shared a breakpoint 
      at 2p21-22, and three others shared a dicentric chromosome 9 or an isochromosome 
      9q. In contrast to the near-diploidy of the low-grade lesions, a high-grade 
      lesion and its nodal metastasis were markedly aneuploid, revealed loss of VHL by 
      fluorescence in situ hybridization (FISH), and contained recurrent unbalanced 
      translocations and losses of chromosome arms 2q, 3p, 4q, 9p, 14q, and 19p as 
      demonstrated by comparative genomic hybridization (CGH). By combining SKY, CGH, 
      and FISH of multiple tumors from the same VHL kidney, we have begun to identify 
      chromosomal aberrations in the earliest stages of VHL-related renal cell tumors. 
      Our current findings illustrate the cytogenetic heterogeneity of different VHL 
      lesions from the same kidney, which supports the multiclonal origins of 
      hereditary RCCs. Published 2001 Wiley-Liss, Inc.
FAU - Phillips, J L
AU  - Phillips JL
AD  - National Cancer Institute, National Institutes of Health, Bethesda, Maryland 
      20892, USA. phillipj@mail.nih.gov
FAU - Ghadimi, B M
AU  - Ghadimi BM
FAU - Wangsa, D
AU  - Wangsa D
FAU - Padilla-Nash, H
AU  - Padilla-Nash H
FAU - Worrell, R
AU  - Worrell R
FAU - Hewitt, S
AU  - Hewitt S
FAU - Walther, M
AU  - Walther M
FAU - Linehan, W M
AU  - Linehan WM
FAU - Klausner, R D
AU  - Klausner RD
FAU - Ried, T
AU  - Ried T
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
SB  - IM
MH  - Adult
MH  - Carcinoma, Renal Cell/*genetics/pathology/surgery
MH  - Chromosome Aberrations/genetics
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Karyotyping/methods
MH  - Kidney Neoplasms/*genetics/pathology/surgery
MH  - Male
MH  - Middle Aged
MH  - Translocation, Genetic/genetics
MH  - Tumor Cells, Cultured
MH  - von Hippel-Lindau Disease/*genetics/pathology/surgery
EDAT- 2001/04/03 10:00
MHDA- 2001/06/23 10:01
CRDT- 2001/04/03 10:00
PHST- 2001/04/03 10:00 [pubmed]
PHST- 2001/06/23 10:01 [medline]
PHST- 2001/04/03 10:00 [entrez]
AID - 10.1002/gcc.1111 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 2001 May;31(1):1-9. doi: 10.1002/gcc.1111.