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Environ Health Perspect. 1987 December; 76: 147–153.
PMCID: PMC1474469
Research Article

Human hypervariable sequences in risk assessment: rare Ha-ras alleles in cancer patients.

Abstract

A variable tandem repeat (VTR) is responsible for the hyperallelism one kilobase 3' to the human c-Ha-ras-1 (Ha-ras) gene. Thirty-two distinct restriction fragments, comprising 3 allelic classes by frequency of occurrence, have thus far been detected in a sample size of approximately 800 caucasians. Rare Ha-ras alleles, 21 in all, are almost exclusively confined to the genomes of cancer patients (p less than 0.001). From our data we have computed the relative cancer risk associated with possession of a rare Ha-ras allele to be 27. To understand the molecular basis for this phenomenon, we have begun to clone Ha-ras fragments from nontumor DNA of cancer patients. We report here the weak activation, as detected by transfection and transformation of NIH 3T3 mouse cells, of two Ha-ras genes which were obtained from lymphocyte DNA of a melanoma patient. We have mapped the regions that confer this transforming activity to the fragment containing the VTR in one Ha-ras clone and the fragment containing gene coding sequences in the other.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Krontiris TG, DiMartino NA, Colb M, Parkinson DR. Unique allelic restriction fragments of the human Ha-ras locus in leukocyte and tumour DNAs of cancer patients. Nature. 313(6001):369–374. [PubMed]
  • Krontiris TG, DiMartino NA, Colb M, Mitcheson HD, Parkinson DR. Human restriction fragment length polymorphisms and cancer risk assessment. J Cell Biochem. 1986;30(4):319–329. [PubMed]
  • Lidereau R, Escot C, Theillet C, Champeme MH, Brunet M, Gest J, Callahan R. High frequency of rare alleles of the human c-Ha-ras-1 proto-oncogene in breast cancer patients. J Natl Cancer Inst. 1986 Sep;77(3):697–701. [PubMed]
  • Thein SL, Oscier DG, Flint J, Wainscoat JS. Ha-ras hypervariable alleles in myelodysplasia. Nature. 1986 May 1;321(6065):84–85. [PubMed]
  • Heighway J, Thatcher N, Cerny T, Hasleton PS. Genetic predisposition to human lung cancer. Br J Cancer. 1986 Apr;53(4):453–457. [PMC free article] [PubMed]
  • Gerhard DS, Dracopoli NC, Bale SJ, Houghton AN, Watkins P, Payne CE, Greene MH, Housman DE. Evidence against Ha-ras-1 involvement in sporadic and familial melanoma. Nature. 1987 Jan 1;325(6099):73–75. [PubMed]
  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. [PubMed]
  • Loenen WA, Brammar WJ. A bacteriophage lambda vector for cloning large DNA fragments made with several restriction enzymes. Gene. 1980 Aug;10(3):249–259. [PubMed]
  • Benton WD, Davis RW. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. [PubMed]
  • Chang EH, Furth ME, Scolnick EM, Lowy DR. Tumorigenic transformation of mammalian cells induced by a normal human gene homologous to the oncogene of Harvey murine sarcoma virus. Nature. 1982 Jun 10;297(5866):479–483. [PubMed]
  • Maniatis T, Jeffrey A, Kleid DG. Nucleotide sequence of the rightward operator of phage lambda. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1184–1188. [PubMed]
  • Graham FL, van der Eb AJ. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. [PubMed]
  • Shih C, Weinberg RA. Isolation of a transforming sequence from a human bladder carcinoma cell line. Cell. 1982 May;29(1):161–169. [PubMed]
  • Rodenhuis S, Bos JL, Slater RM, Behrendt H, van 't Veer M, Smets LA. Absence of oncogene amplifications and occasional activation of N-ras in lymphoblastic leukemia of childhood. Blood. 1986 Jun;67(6):1698–1704. [PubMed]
  • Varmus HE. The molecular genetics of cellular oncogenes. Annu Rev Genet. 1984;18:553–612. [PubMed]

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