MUTATIONAL SPECTRUM IN THE P53 GENE IN BLADDER-TUMORS FROM THE ENDEMIC AREA OF BLACK FOOT DISEASE IN TAIWAN
MUTATIONAL SPECTRUM IN THE P53 GENE IN BLADDER-TUMORS FROM THE ENDEMIC AREA OF BLACK FOOT DISEASE IN TAIWAN
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DOI：
10.1093/carcin/15.6.1085
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发表时间：
1994-06-01
期刊：
影响因子：
4.7
通讯作者：
JONES, PA
中科院分区：
文献类型：
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作者：
SHIBATA, A;OHNESEIT, PF;JONES, PA
据报道，在台湾西南海岸的“黑脚病”流行地区，膀胱癌的风险增加，这可能与自流井水中的高砷含量有关。从这个流行地区的13个尿路上皮肿瘤进行了检查，在外显子5 - 8的p53基因的突变，以确定可能的外源性因素在DNA水平上的影响。在显微切割肿瘤后从存档组织中提取DNA，并通过PCR-SSCP（基于聚合酶链反应的单链构象多态性）进行分析，然后直接测序。8例（62%）显示突变，观察到的10个点突变中有9个是转换。突变的类型和位置没有显着不同时，与光谱的p53突变以前报告的移行细胞癌（TCC）。然而，其中两个突变是密码子175处的CGC -> CAC碱基变化，这是许多肿瘤类型的突变热点，但以前在TCC中未报道，除了与炎症因子相关的病例。研究发现，其中三个肿瘤含有双重突变，这是人类癌症中相对罕见的致突变事件。我们的研究结果表明，在黑脚病地区的膀胱癌的高风险负责的代理人可能通过炎症为基础的机制，增加了每个诱变事件的DNA损伤量。
An elevated risk of bladder cancer has been reported in the endemic region of 'black foot disease' on the southwest coast of Taiwan and may be related to high arsenic levels in artesian well water. Thirteen urothelial tumors from this endemic region were examined for mutations in exons 5 - 8 of the p53 gene to identify the effects of possible exogenous factors at the DNA level. DNA was extracted from archival tissue after microdissection of tumors and analyzed by PCR-SSCP (polymerase chain reaction-based single strand conformation polymorphism), followed by direct sequencing. Eight cases (62%) showed mutations and 9 of the 10 point mutations observed were transitions. The type and position of the mutations were not significantly different when compared with the spectra of p53 mutations previously reported for transitional cell carcinomas (TCCs). However, two of the mutations were CGC --> CAC base changes at codon 175, a mutational hotspot for many tumor types but previously unreported in TCCs except in cases associated with inflammatory agents. Three of the tumors examined were found to contain double mutations, a relatively rare mutagenic event in human cancers. Our results suggest that the agents responsible for the high risk of bladder cancer in the black foot disease region may operate through an inflammation-based mechanism which increases the amount of DNA damage per mutagenic event.