Search tips
Search criteria 


Logo of narLink to Publisher's site
Nucleic Acids Res. 1983 October 11; 11(19): 6883–6894.
PMCID: PMC326421

The 5-methylcytosine content of DNA from human tumors.


The over-all 5-methylcytosine (m5C) content of DNA from normal tissues varies considerably in a tissue-specific manner. By high-performance liquid chromatography, we have examined the m5C contents of enzymatic digests of DNA from 103 human tumors including benign, primary malignant and secondary malignant neoplasms. The diversity and large number of these tumor samples allowed us to compare the range of DNA methylation levels from neoplastic tissues to that of normal tissues from humans. Most of the metastatic neoplasms had significantly lower genomic m5C contents than did most of the benign neoplasms or normal tissues. The percentage of primary malignancies with hypomethylated DNA was intermediate between those of metastases and benign neoplasms. These findings might reflect an involvement of extensive demethylation of DNA in tumor progression. Such demethylation could be a source of the continually generated cellular diversity associated with cancer.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Vanyushin BF, Mazin AL, Vasilyev VK, Belozersky AN. The content of 5-methylcytosine in animal DNA: the species and tissue specificity. Biochim Biophys Acta. 1973 Mar 28;299(3):397–403. [PubMed]
  • Kappler JW. The 5-methylcytosine content of DNA: tissue specificity. J Cell Physiol. 1971 Aug;78(1):33–36. [PubMed]
  • Ehrlich M, Gama-Sosa MA, Huang LH, Midgett RM, Kuo KC, McCune RA, Gehrke C. Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells. Nucleic Acids Res. 1982 Apr 24;10(8):2709–2721. [PMC free article] [PubMed]
  • Gama-Sosa MA, Midgett RM, Slagel VA, Githens S, Kuo KC, Gehrke CW, Ehrlich M. Tissue-specific differences in DNA methylation in various mammals. Biochim Biophys Acta. 1983 Jun 24;740(2):212–219. [PubMed]
  • Ehrlich M, Wang RY. 5-Methylcytosine in eukaryotic DNA. Science. 1981 Jun 19;212(4501):1350–1357. [PubMed]
  • Doerfler W. DNA methylation--a regulatory signal in eukaryotic gene expression. J Gen Virol. 1981 Nov;57(Pt 1):1–20. [PubMed]
  • Stein R, Razin A, Cedar H. In vitro methylation of the hamster adenine phosphoribosyltransferase gene inhibits its expression in mouse L cells. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3418–3422. [PubMed]
  • Jähner D, Stuhlmann H, Stewart CL, Harbers K, Löhler J, Simon I, Jaenisch R. De novo methylation and expression of retroviral genomes during mouse embryogenesis. Nature. 1982 Aug 12;298(5875):623–628. [PubMed]
  • Christy B, Scangos G. Expression of transferred thymidine kinase genes is controlled by methylation. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6299–6303. [PubMed]
  • Creusot F, Acs G, Christman JK. Inhibition of DNA methyltransferase and induction of Friend erythroleukemia cell differentiation by 5-azacytidine and 5-aza-2'-deoxycytidine. J Biol Chem. 1982 Feb 25;257(4):2041–2048. [PubMed]
  • Compere SJ, Palmiter RD. DNA methylation controls the inducibility of the mouse metallothionein-I gene lymphoid cells. Cell. 1981 Jul;25(1):233–240. [PubMed]
  • Mermod JJ, Bourgeois S, Defer N, Crépin M. Demethylation and expression of murine mammary tumor proviruses in mouse thymoma cell lines. Proc Natl Acad Sci U S A. 1983 Jan;80(1):110–114. [PubMed]
  • Jones PA, Taylor SM. Cellular differentiation, cytidine analogs and DNA methylation. Cell. 1980 May;20(1):85–93. [PubMed]
  • Feinberg AP, Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature. 1983 Jan 6;301(5895):89–92. [PubMed]
  • Feinberg AP, Vogelstein B. Hypomethylation of ras oncogenes in primary human cancers. Biochem Biophys Res Commun. 1983 Feb 28;111(1):47–54. [PubMed]
  • Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967 Jun 14;26(2):365–369. [PubMed]
  • Gama-Sosa MA, Wang RY, Kuo KC, Gehrke CW, Ehrlich M. The 5-methylcytosine content of highly repeated sequences in human DNA. Nucleic Acids Res. 1983 May 25;11(10):3087–3095. [PMC free article] [PubMed]
  • Kuo KC, McCune RA, Gehrke CW, Midgett R, Ehrlich M. Quantitative reversed-phase high performance liquid chromatographic determination of major and modified deoxyribonucleosides in DNA. Nucleic Acids Res. 1980 Oct 24;8(20):4763–4776. [PMC free article] [PubMed]
  • Bagshawe KD. Some facets of trophoblastic neoplasia in man. J Reprod Fertil Suppl. 1982 Nov;31:175–179. [PubMed]
  • van der Ploeg LH, Flavell RA. DNA methylation in the human gamma delta beta-globin locus in erythroid and nonerythroid tissues. Cell. 1980 Apr;19(4):947–958. [PubMed]
  • Cooper DN, Taggart MH, Bird AP. Unmethylated domains in vertebrate DNA. Nucleic Acids Res. 1983 Feb 11;11(3):647–658. [PMC free article] [PubMed]
  • Busslinger M, deBoer E, Wright S, Grosveld FG, Flavell RA. The sequence GGCmCGG is resistant to MspI cleavage. Nucleic Acids Res. 1983 Jun 11;11(11):3559–3569. [PMC free article] [PubMed]
  • Keshet E, Cedar H. Effect of CpG methylation on Msp I. Nucleic Acids Res. 1983 Jun 11;11(11):3571–3580. [PMC free article] [PubMed]
  • Barlogie B, Drewinko B, Schumann J, Göhde W, Dosik G, Latreille J, Johnston DA, Freireich EJ. Cellular DNA content as a marker of neoplasia in man. Am J Med. 1980 Aug;69(2):195–203. [PubMed]
  • Lapeyre JN, Becker FF. 5-Methylcytosine content of nuclear DNA during chemical hepatocarcinogenesis and in carcinomas which result. Biochem Biophys Res Commun. 1979 Apr 13;87(3):698–705. [PubMed]
  • Fidler IJ, Hart IR. Biological diversity in metastatic neoplasms: origins and implications. Science. 1982 Sep 10;217(4564):998–1003. [PubMed]
  • Wang RY, Shedlarski JG, Farber MB, Kuebbing D, Ehrlich M. Two sequence-specific endonucleases from Xanthomonas oryzae. Characterization and unusual properties. Biochim Biophys Acta. 1980 Feb 29;606(2):371–385. [PubMed]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press