Early p53 mutations in nondysplastic Barrett's tissue detected by the restriction site mutation (RSM) methodology.

Early p53 mutations in nondysplastic Barrett's tissue detected by the restriction site mutation (RSM) methodology.
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DOI:
10.1038/sj.bjc.6600891
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发表时间:
2003-04-22
影响因子:
8.8
通讯作者:
--
中科院分区:
医学1区
文献类型:
--
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巴雷特食管是一种恶性前病变,其发病率正在急剧上升。目前迫切需要分子标记来识别癌症进展风险最高的巴雷特患者。为此,我们使用了一种快速分子技术,限制性内切位点突变(RSM),检测无癌患者Barrett癌前组织中p53肿瘤抑制基因的低频突变。总共有38例经内镜诊断为Barrett's的患者具有Barrett's进展的一系列组织学阶段,加上4例没有Barrett's食管的对照患者,分析了早期p53突变。对这些患者的组织样本(共93个样本)进行分析,发现在热点密码子175、213、248、249、282处存在低频p53突变。总共,38名巴雷特患者中有13名至少在一个样本中具有p53突变(4名对照患者中没有突变)。虽然没有发现统计学意义上的相关性,但p53突变反映了Barrett患者的组织学进展,其中30%的化生患者(P=0.4)和低级别发育不良患者(P=0.33)以及45%的高级别发育不良患者(P=0.15)存在p53突变。检测到的p53突变主要是CpG位点的GC到AT转变。
Barrett's oesophagus is a premalignant condition whose incidence is rising dramatically. Molecular markers are urgently needed to identify Barrett's patients at the highest risk of cancer progression. To this end, we have used a rapid molecular technique, restriction site mutation (RSM), to detect low-frequency mutations in the p53 tumour suppressor gene in premalignant Barrett's tissues of cancer-free patients. In total, 38 endoscopically diagnosed Barrett's patients with a range of histological stages of Barrett's progression, plus four control patients without Barrett's oesophagus, were analysed for early p53 mutations. Tissue samples taken from these patients (93 samples in total) were analysed for the presence of low-frequency p53 mutations at hotspot codons: 175, 213, 248, 249, 282. In total, 13 of the 38 Barrett's patients were shown to possess a p53 mutation in at least one sample (no mutations in the four control patients). Although no statistically significant associations were found, p53 mutations reflected histological progression in Barrett's patients with p53 mutations found in 30% of metaplasia patients (P=0.4) and low-grade dysplasia patients (P=0.33) and 45% of high-grade dysplasia patients (P=0.15). Detected p53 mutations were mainly GC to AT transitions at CpG sites.
DOI: 10.1016/s1383-5718(01)00281-9
发表时间: 2001-11-15
影响因子: 1.9
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影响因子: 6
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发表时间: 1996-03-22
期刊: SCIENCE
影响因子: 56.9
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通讯作者: VandeVoude, GF
DOI: 10.1038/bjc.1998.44
发表时间: 1998
影响因子: 8.8
作者:
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