Genomewide DNA hypomethylation is associated with alterations on chromosome 8 in prostate carcinoma
Genomewide DNA hypomethylation is associated with alterations on chromosome 8 in prostate carcinoma
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DOI：
10.1002/gcc.10092
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发表时间：
2002-09-01
影响因子：
3.7
通讯作者：
Visakorpi, T
中科院分区：
文献类型：
--
作者：
Schulz, WA;Elo, JP;Visakorpi, T
为了阐明全基因组DNA低甲基化和染色体不稳定性之间的关系，55例前列腺癌标本进行了分析的低甲基化程度的Southern印迹分析的LINE-1序列甲基化和损失或获得的染色体材料的比较基因组杂交。17例（31%）肿瘤显示出强烈的DNA低甲基化，而4例（7%）显示出轻微的低甲基化，其余肿瘤为正常水平的甲基化。在34例癌中观察到染色体畸变。最常见的染色体改变为13 q缺失18例，8 p（缺失）或8 q（获得）畸变16例。染色体丢失或获得的存在与强低甲基化的存在显著相关。一个显着的相关性（P = 0.00001），观察8号染色体畸变和低甲基化之间，而DNA低甲基化和损失的13 q之间没有关联。DNA低甲基化和转移瘤的存在之间的关联是统计学上显著的（P = 0.044），并且染色体改变和DNA低甲基化倾向于在更高阶段的肿瘤中更频繁。总之，数据表明低甲基化与前列腺癌中的染色体不稳定性相关。特别是，8号染色体的改变和全基因组低甲基化之间惊人的强关联被发现，这种关联表明，在前列腺癌中，DNA低甲基化和8号染色体的改变可能在机械上相互联系。(C)2002 Wiley-Liss，Inc.
To elucidate the relationship between genomewide DNA hypomethylation and chromosome instability, 55 prostate carcinoma specimens were analyzed for extent of hypomethylation by Southern blot analysis of LINE-1 sequence methylation and for loss or gain of chromosomal material by comparative genomic hybridization. Seventeen (31%) tumors showed strong hypomethylation of DNA, whereas four (7%) displayed slight hypomethylation and the rest of the tumors normal-level methylation. Chromosomal aberrations were observed in 34 carcinomas. The most frequent chromosomal alterations were loss of 13q in 18 cases and aberrations in 8p (loss) or 8q (gain) in 16 cases. The presence of chromosomal loss or gain was significantly associated with the presence of strong hypomethylation. A striking correlation (P = 0.00001) was observed between aberrations on chromosome 8 and hypomethylation, whereas no association was seen between DNA hypomethylation and loss of 13q. The association between DNA hypomethylation and the presence of metastases was statistically significant (P = 0.044), and both chromosomal alterations and DNA hypomethylation tended to be more frequent in higher-stage tumors, In conclusion, the data indicate that hypomethylation is associated with chromosomal instability in prostate cancer. Specifically, a surprisingly strong association between alterations on chromosome 8 and genomewide hypomethylation was found. This association suggests that DNA hypomethylation and alterations in chromosome 8 may be mechanistically linked to each other in prostate carcinoma. (C) 2002 Wiley-Liss, Inc.