de Bustros A, Nelkin B D, Silverman A, Ehrlich G, Poiesz B, Baylin S B
Oncology Center, School of Medicine, Johns Hopkins University, Baltimore, MD 21215.
Proc Natl Acad Sci U S A. 1988 Aug;85(15):5693-7. doi: 10.1073/pnas.85.15.5693.
Inactivation of normally expressed genes may play a role in the formation and/or progression of human cancers. Methylation of cytosine in DNA could potentially participate in such alterations of gene expression. Abnormalities in DNA methylation are a consistent feature of human neoplasms, and we now show that these include not only previously recognized widespread genomic hypomethylation, but also regional increases in gene methylation. A hot spot for abnormal methylation of C + G-rich areas has been detected on the short arm of chromosome 11 in an area known to harbor tumor suppressor genes. This change occurs consistently in common forms of human cancer and appears early during the transformation of cells with viruses including members of the human T-cell leukemia (HTLV) family. Furthermore, in one chromosome 11 gene examined, calcitonin, the increased methylation in somatic tumor cells coincides with the presence of an "inactive" chromatin pattern in the transcriptional regulatory area. The increased regional DNA methylation demonstrated may then participate in or mark chromosomal changes associated with gene inactivation events that are central to the genesis and/or progression of human cancers.
正常表达基因的失活可能在人类癌症的形成和/或发展中起作用。DNA中胞嘧啶的甲基化可能参与基因表达的此类改变。DNA甲基化异常是人类肿瘤的一个一致特征，我们现在表明，这些异常不仅包括先前公认的广泛基因组低甲基化，还包括基因甲基化的区域增加。在11号染色体短臂上一个已知含有肿瘤抑制基因的区域，检测到富含C+G区域异常甲基化的一个热点。这种变化在人类常见癌症形式中持续出现，并在包括人类T细胞白血病（HTLV）家族成员在内的病毒转化细胞的早期出现。此外，在所检测的一个11号染色体基因降钙素中，体细胞肿瘤细胞中甲基化增加与转录调控区域中“无活性”染色质模式的存在一致。所显示的区域DNA甲基化增加可能参与或标记与基因失活事件相关的染色体变化，而这些事件是人类癌症发生和/或发展的核心。
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