Home LiteratureArticle Details
PMID: 3865197 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Loss of the normal N-ras allele in a mouse thymic lymphoma induced by a chemical carcinogen.

Guerrero I, Villasante A, Corces V, Pellicer A

Abstract

Young mice injected with the carcinogen N-nitroso-N-methylurea develop thymic lymphomas 2-4 months later. We previously have shown that these tumors frequently contain an activated N-ras gene that can transform rodent fibroblasts in vitro. We report here the intron/exon structure of such an activated N-ras gene and the sequence of its four coding exons. A single nucleotide change is responsible for the transforming alteration, a C----A transversion in the first base of codon 61. Through the use of synthetic oligonucleotides as hybridization probes, we show that this tumor lacks the normal allele of the N-ras gene. The implications of this finding for oncogene dominance are discussed.

MeSH Terms
Alleles Animals Base Sequence Brain/physiology Chromosome Mapping Genes, Dominant Lymphoma/chemically induced,genetics Methylnitrosourea Mice Mutation Proto-Oncogenes Thymus Neoplasms/chemically induced,genetics
Chemicals
Methylnitrosourea
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Guerrero I
Villasante A
Corces V
Pellicer A
References (38)
38 references, click to expand
  1. Identification of a normal vertebrate cell protein related to the p21 src of Harvey murine sarcoma virus.
    Virology. 1980 Oct 30;106(2):292-300 PMID: 6254252
  2. Sequencing end-labeled DNA with base-specific chemical cleavages.
    Methods Enzymol. 1980;65(1):499-560 PMID: 6246368
  3. A system for shotgun DNA sequencing.
    Nucleic Acids Res. 1981 Jan 24;9(2):309-21 PMID: 6259625
  4. Transforming activity of human tumor DNAs.
    Proc Natl Acad Sci U S A. 1981 Feb;78(2):1181-4 PMID: 6940134
  5. The p21 src genes of Harvey and Kirsten sarcoma viruses originate from divergent members of a family of normal vertebrate genes.
    Nature. 1981 Aug 6;292(5823):506-11 PMID: 6265801
  6. Human EJ bladder carcinoma oncogene is homologue of Harvey sarcoma virus ras gene.
    Nature. 1982 Jun 10;297(5866):474-8 PMID: 6283357
  7. T24 human bladder carcinoma oncogene is an activated form of the normal human homologue of BALB- and Harvey-MSV transforming genes.
    Nature. 1982 Jul 22;298(5872):343-7 PMID: 6283384
  8. Transforming genes of human bladder and lung carcinoma cell lines are homologous to the ras genes of Harvey and Kirsten sarcoma viruses.
    Proc Natl Acad Sci U S A. 1982 Jun;79(11):3637-40 PMID: 6285355
  9. Oncogenes in solid human tumours.
    Nature. 1982 Dec 9;300(5892):539-42 PMID: 7144906
  10. The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers.
    Gene. 1982 Oct;19(3):259-68 PMID: 6295879
  11. Isolation and preliminary characterization of the transforming gene of a human neuroblastoma cell line.
    Proc Natl Acad Sci U S A. 1983 Jan;80(2):383-7 PMID: 6300838
  12. Mouse skin carcinomas induced in vivo by chemical carcinogens have a transforming Harvey-ras oncogene.
    Nature. 1983 May 5-11;303(5912):72-4 PMID: 6843661
  13. alpha 1-antitrypsin deficiency detection by direct analysis of the mutation in the gene.
    Nature. 1983 Jul 21-27;304(5923):230-4 PMID: 6306478
  14. Activation of Ki-ras2 gene in human colon and lung carcinomas by two different point mutations.
    Nature. 1983 Aug 11-17;304(5926):507-13 PMID: 6308467
  15. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes.
    Nature. 1983 Aug 18-24;304(5927):596-602 PMID: 6308472
  16. Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture.
    Nature. 1983 Aug 18-24;304(5927):602-6 PMID: 6308473
  17. Structure and activation of the human N-ras gene.
    Cell. 1983 Sep;34(2):581-6 PMID: 6616621
  18. Induction of mammary carcinomas in rats by nitroso-methylurea involves malignant activation of H-ras-1 locus by single point mutations.
    Nature. 1983 Dec 15-21;306(5944):658-61 PMID: 6318112
  19. A molecular approach to leukemogenesis: mouse lymphomas contain an activated c-ras oncogene.
    Proc Natl Acad Sci U S A. 1984 Jan;81(1):202-5 PMID: 6582476
  20. Malignant activation of a K-ras oncogene in lung carcinoma but not in normal tissue of the same patient.
    Science. 1984 Feb 17;223(4637):661-4 PMID: 6695174
  21. Transforming ras genes from human melanoma: a manifestation of tumour heterogeneity?
    Nature. 1984 Mar 1-7;308(5954):69-72 PMID: 6700714
  22. Mechanism of activation of an N-ras oncogene of SW-1271 human lung carcinoma cells.
    Proc Natl Acad Sci U S A. 1984 Jun;81(12):3670-4 PMID: 6587382
  23. An activated rasN gene: detected in late but not early passage human PA1 teratocarcinoma cells.
    Science. 1984 Aug 10;225(4662):643-5 PMID: 6740333
  24. Mechanism of activation of an N-ras gene in the human fibrosarcoma cell line HT1080.
    EMBO J. 1984 Jun;3(6):1321-6 PMID: 6086315
  25. Malignant transformation of early passage rodent cells by a single mutated human oncogene.
    Nature. 1984 Aug 9-15;310(5977):469-75 PMID: 6462235
  26. A position 12-activated H-ras oncogene in all HS578T mammary carcinosarcoma cells but not normal mammary cells of the same patient.
    Proc Natl Acad Sci U S A. 1984 Sep;81(17):5384-8 PMID: 6089200
  27. Isolation, characterization, and chromosome assignment of mouse N-ras gene from carcinogen-induced thymic lymphoma.
    Science. 1984 Sep 7;225(4666):1041-3 PMID: 6089339
  28. Activation of a c-K-ras oncogene by somatic mutation in mouse lymphomas induced by gamma radiation.
    Science. 1984 Sep 14;225(4667):1159-62 PMID: 6474169
  29. Three different mutations in codon 61 of the human N-ras gene detected by synthetic oligonucleotide hybridization.
    Nucleic Acids Res. 1984 Dec 11;12(23):9155-63 PMID: 6595642
  30. Unique allelic restriction fragments of the human Ha-ras locus in leukocyte and tumour DNAs of cancer patients.
    Nature. 1985 Jan 31-Feb 6;313(6001):369-74 PMID: 2578622
  31. The molecular genetics of cellular oncogenes.
    Annu Rev Genet. 1984;18:553-612 PMID: 6397126
  32. Direct mutagenesis of Ha-ras-1 oncogenes by N-nitroso-N-methylurea during initiation of mammary carcinogenesis in rats.
    Nature. 1985 May 30-Jun 5;315(6018):382-5 PMID: 3923365
  33. Human-tumor-derived cell lines contain common and different transforming genes.
    Cell. 1981 Dec;27(3 Pt 2):467-76 PMID: 6101201
  34. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  35. Comparison of the genomic organization of Kirsten and Harvey sarcoma viruses.
    J Virol. 1978 Jul;27(1):45-55 PMID: 211254
  36. Structure and genomic organization of the mouse dihydrofolate reductase gene.
    Cell. 1980 Feb;19(2):355-64 PMID: 6244105
  37. Detection of specific sequences among DNA fragments separated by gel electrophoresis.
    J Mol Biol. 1975 Nov 5;98(3):503-17 PMID: 1195397
  38. Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts.
    Nature. 1981 Mar 19;290(5803):261-4 PMID: 7207618
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1985-12-00
Pages
7810-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC390859
Subset
IM
Grants
NCI NIH HHS · CA16239 · United States
NCI NIH HHS · CA36327 · United States
NIGMS NIH HHS · GM32036 · United States
Databases
GENBANK
M12121, M12122, M12123, M12124
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]