We have developed a powerful technique (representational difference analysis, or RDA) for the comparison of the differences between two complex genomes. By performing RDA on DNA from human tumor cells and the DNA extracted from normal tissue or blood of the same patient, we can derive probes for loci that have undergone genetic alterations including deletions, translocations, inversions, insertions and amplifications in the tumor cells. Moreover, we can detect foreign genomes (such as viral genomes), if any are present. This methodology presents an unparalleled opportunity to discover the genetic lesions that underlie cancer. We propose to apply this methodology to a series of renal cell carcinoma cell lines and paired normal DNA in order to derive probes that detect genetic lesions in such cell lines. These probes will be used to detect similar types of lesions in other human cancers. We shall further attempt to define the critical genes affected by these lesions, and to test them for biological function. Special emphasis will be placed on tumor suppressor genes.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA064534-02
Application #
2107075
Study Section
Pathology B Study Section (PTHB)
Project Start
1994-07-01
Project End
1995-08-31
Budget Start
1995-05-01
Budget End
1995-08-31
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724
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Ozoren, N; Fisher, M J; Kim, K et al. (2000) Homozygous deletion of the death receptor DR4 gene in a nasopharyngeal cancer cell line is associated with TRAIL resistance. Int J Oncol 16:917-25
Eyaid, W M; Clough, M V; Root, H et al. (1998) Physical mapping of the nail patella syndrome interval at 9q34: ordering of STSs and ESTs. Hum Genet 103:525-6