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Activated protooncogenes in human lung tumors from smokers

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America; (United States)
; ; ; ;  [1];  [2];  [3];  [4]
  1. National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States)
  2. Beth Israel Medical Center, New York, NY (United States)
  3. New York Univ., NY (United States)
  4. Duke Univ., Durham, NC (United States)
Fourteen primary human lung tumor DNAs from smokers were analyzed for transforming activity by two DNA transfection assays. Activated protooncogenes were detected in 3 of 11 tumor DNAs by the NIK 3T3 focus assay, whereas activated protooncogenes were detected in 11 of 13 tumor DNAs by the NIH 3T3 cotransfection-nude mouse tumorigenicity assay. K- or NRAS genes activated by point mutation at codons 12 or 61 were detected in a large cell carcinoma, a squamous cell carcinoma, and 5 adenocarcinomas. An HRAS oncogene activated by a different mechanism was detected in an epidermoid carcinoma. One adenocarcinoma was found to contain an activated RAF gene. Two unidentified transforming genes were detected in a squamous cell carcinoma DNA and two adenocarcinoma DNAs. Eight of 10 lung adenocarcinomas that had formed metastases at the time of surgery were found to contain RAS oncogenes. No significant increase in metastasis was observed in the lung adenocarcinomas that contained one of more 6-kilobase EcoRI alleles of the LYMC gene. Overall, 12 of 14 (86%) of the lung tumor DNAs from smokers were found to contain activated protooncogenes. RAS oncogenes appear to play a role in the development of metastases in lung adenocarcinomas.
OSTI ID:
6161153
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:4; ISSN 0027-8424; ISSN PNASA
Country of Publication:
United States
Language:
English

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