DNA hypomethylation on pericentromeric satellite regions significantly correlates with loss of heterozygosity on chromosome 9 in urothelial carcinomas
DNA hypomethylation on pericentromeric satellite regions significantly correlates with loss of heterozygosity on chromosome 9 in urothelial carcinomas
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DOI：
10.1097/01.ju.0000141577.98902.49
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发表时间：
2005-01-01
影响因子：
6.6
通讯作者：
Hirohashi, S
中科院分区：
文献类型：
--
作者：
Nakagawa, T;Kanai, Y;Hirohashi, S
目的：DNA甲基化在基因组稳定性中起重要作用。因此，中心粒周围卫星区的DNA低甲基化可能通过异染色质去浓缩和染色体重组增强而引起染色体不稳定。我们阐明了异常DNA甲基化在尿路上皮癌发生过程中的意义。材料与方法：采用Southern blotting检测卫星2和3的DNA甲基化状态，并利用6个微卫星标记（D9S775、D9S925、D9S304、D9S303、D9S283和D9S747）检测9号染色体的等位基因状态。结果：2例（7%）非癌组织检测到卫星2和卫星3 DNA低甲基化，0例（0%）非癌组织检测到卫星2和卫星3 DNA低甲基化，11例（41%）尿路上皮癌组织检测到卫星2和卫星3 DNA低甲基化，12例尿路上皮癌组织检测到卫星2和卫星3 DNA低甲基化。尿路上皮癌DNA低甲基化分别与卫星2和卫星3的组织学分级（p = 0.0012和0.0043）、浸润深度（p = 0.0055和0.0228）和形态结构（乳头状vs结节状，p = 0.0161和0.0297）显著相关。在14例（52%）尿路上皮癌中检测到9号染色体至少1个位点的杂合性缺失。卫星2 （p = 0.0098）和3 （p = 0.0034）上的DNA低甲基化与9号染色体杂合性缺失显著相关。结论：中心点周围卫星区DNA低甲基化可能通过诱导9号染色体杂合性缺失参与尿路上皮癌的发生发展。
Purpose: DNA methylation has important roles in genomic stability. Accordingly DNA hypomethylation on pericentromeric satellite regions may induce chromosomal instability through heterochromatin decondensation and chromosomal recombination enhancement. We elucidated the significance of aberrant DNA methylation on pericentromeric satellite regions during urothelial carcinogenesis.Materials and Methods: We examined DNA methylation status on satellites 2 and 3 by Southern blotting and determined the allelic status of chromosome 9 using 6 microsatellite markers (D9S775, D9S925, D9S304, D9S303, D9S283 and D9S747) in 27 transitional cell carcinomas of the bladder, ureter or renal pelvis and corresponding noncancerous tissues.Results: DNA hypomethylation on satellites 2 and 3 was detected in 2 (7%) and no (0%) noncancerous tissues, and in 11 (41%) and 12 (44%) urothelial carcinomas, respectively. DNA hypomethylation in urothelial carcinomas significantly correlated with histological grade (p = 0.0012 and 0.0043), invasion depth (p = 0.0055 and 0.0228) and morphological structure (papillary vs nodular, p = 0.0161 and 0.0297) for satellites 2 and 3, respectively. Loss of heterozygosity on at least 1 locus of chromosome 9 was detected in 14 urothelial carcinomas (52%). DNA hypomethylation on satellites 2 (p = 0.0098) and 3 (p = 0.0034) significantly correlated with loss of heterozygosity on chromosome 9.Conclusions: DNA hypomethylation on pericentromeric satellite regions may participate in the development and progression of urothelial carcinomas by inducing loss of heterozygosity on chromosome 9.