DISTINCT HYPERMETHYLATION PATTERNS OCCUR AT ALTERED CHROMOSOME LOCI IN HUMAN LUNG AND COLON CANCER
DISTINCT HYPERMETHYLATION PATTERNS OCCUR AT ALTERED CHROMOSOME LOCI IN HUMAN LUNG AND COLON CANCER
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DOI：
10.1073/pnas.89.5.1929
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发表时间：
1992-03-01
影响因子：
11.1
通讯作者：
BAYLIN, SB
中科院分区：
文献类型：
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作者：
MAKOS, M;NELKIN, BD;BAYLIN, SB
在肿瘤细胞中，DNA甲基化的区域性增加发生在通常未甲基化的富含胞嘧啶的区域。这些变化可能会改变染色质结构，导致基因转录或DNA不稳定。我们现在表明，在人类肺癌和结肠癌DNA中，这样一个区域的超甲基化始终发生在染色体17 p上，该区域在两种肿瘤类型中经常降低为纯合性。在结肠瘤形成的进展阶段，这种甲基化变化的程度增加，并在17 p上的等位基因丢失之前，这是结肠癌的特征。我们还表明，在染色体3p区域甲基化可能非随机伴随染色体的变化，在人类肿瘤。在小细胞肺癌DNA中，两个3p基因座的甲基化增加是一致的，这两个基因座在该肿瘤中不断降低为纯合性，但在结肠癌DNA中没有观察到，其中这些基因座很少发生结构改变。
Regional increases in DNA methylation occur in normally unmethylated cytosine-rich areas in neoplastic cells. These changes could potentially alter chromatin structure to inactivate gene transcription or generate DNA instability. We now show that, in human lung and colon cancer DNA, hypermethylation of such a region consistently occurs on chromosome 17p in an area that is frequently reduced to homozygosity in both tumor types. Over the progression stages of colon neoplasia, this methylation change increases in extent and precedes the allelic losses on 17p that are characteristic of colon carcinomas. We also show on chromosome 3p that regional hypermethylation may nonrandomly accompany chromosome changes in human neoplasia. Increased methylation is consistent in small-cell lung carcinoma DNA at two 3p loci that are constantly reduced to homozygosity in this tumor, but it is not seen in colon cancer DNA, in which these loci are infrequently structurally altered.