Gama-Sosa M A, Slagel V A, Trewyn R W, Oxenhandler R, Kuo K C, Gehrke C W, Ehrlich M
Nucleic Acids Res. 1983 Oct 11;11(19):6883-94. doi: 10.1093/nar/11.19.6883.
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.
正常组织DNA的总体5-甲基胞嘧啶（m5C）含量以组织特异性方式存在很大差异。通过高效液相色谱法，我们检测了来自103个人类肿瘤（包括良性、原发性恶性和继发性恶性肿瘤）的DNA酶消化产物中的m5C含量。这些肿瘤样本的多样性和大量性使我们能够比较肿瘤组织与人类正常组织的DNA甲基化水平范围。大多数转移性肿瘤的基因组m5C含量明显低于大多数良性肿瘤或正常组织。DNA低甲基化的原发性恶性肿瘤的百分比介于转移瘤和良性肿瘤之间。这些发现可能反映了DNA广泛去甲基化参与肿瘤进展。这种去甲基化可能是与癌症相关的持续产生的细胞多样性的一个来源。
