We have been analyzing the oncogene activation process in thymic lymphomas developed in mice after carcinogen and radiation induction. We have identified the oncogenes activated as belonging to the ras family, the N-ras in carcinogen-induced tumors, and K-ras in the thymomas caused by radiation. We proceeded to isolate the activated N-ras oncogene and to study its structure through restriction mapping in concert with transfection assays. This allowed us to approximately localize the ends of the gene. A specific fragment obtained from the clone has been used as a probe to assign the N-ras gene to mouse chromosome 3. We also have cloned a piece containing the first exon of the K-ras gene activated in a radiation-induced tumor; and using recombinant constructs with the second, third, and fourth exons of a normal human H-ras gene, we have demonstrated that the transforming activity lies in that piece. Subsequent sequence of the first exon comparing the transformant gene with the normal one isolated from brain DNA from the same mouse that developed the tumor shows only a base change of G to A that will turn a glycin into an aspartic acid in the p21 protein. Synthesis of an oligonucleotide and differential hybridization with it to the thymoma DNA has confirmed that the mutation is present in the tumor. (X)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA036327-03
Application #
3173879
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1984-01-01
Project End
1986-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
New York University
Department
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012
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Perez de Castro, Ignacio; Diaz, Roberto; Malumbres, Marcos et al. (2003) Mice deficient for N-ras: impaired antiviral immune response and T-cell function. Cancer Res 63:1615-22

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