Molecular genetic analysis of surveillance biopsy samples from Barrett's mucosa -: Significance of sampling
Molecular genetic analysis of surveillance biopsy samples from Barrett's mucosa -: Significance of sampling
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DOI：
10.1016/j.prp.2007.12.011
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发表时间：
2008-01-01
影响因子：
2.8
通讯作者：
Heinmoeller, Ernst
中科院分区：
文献类型：
--
作者：
Werther, Meike;Saure, Christoph;Heinmoeller, Ernst
我们的目的是确定频谱和累积的突变监测活检从巴雷特的粘膜个别patients.We进行杂合性丢失（洛）分析6个最近描述的肿瘤抑制基因相关的癌发生的巴雷特腺癌从激光显微解剖，石蜡包埋活检样本的巴雷特粘膜没有或有低度异型增生的变化。在监测项目期间，从26名患者中采集了118份活检样本，时间间隔为6至51个月，我们发现洛缺失事件至少在51个月的时间间隔内没有显著增加。在两名患者中，Barrett腺癌在首次诊断Barrett粘膜后6个月被诊断。26例患者中有6例未出现洛合性丢失。其余患者在随访期间表现出显著的洛缺失模式和活检样本中的累积变化。从我们的微卫星标记物组中，我们无法确定一个单一的替代标记物，可以作为一个潜在的生物标志物，表明进展为巴雷特腺癌的风险增加。然而，洛组合，特别是APC/p16（INK 4）或APC/p53，值得注意的推定的生物标志物在未来的study.Our研究结果提出了重要的问题，除了抽样的影响，特别是关于从巴雷特的粘膜活检的数量在巴雷特的粘膜突变的生物动力学。(C)2008年Elsevier GmbH。All rights reserved.
Our aim was to determine the spectrum and accumulation of mutations in surveillance biopsies from Barrett's mucosa of individual patients during follow-up.We performed loss of heterozygosity (LOH) analysis of six recently described tumor suppressor genes relevant for the carcinogenesis of Barrett's adenocarcinoma from laser-microdissected, paraffin-embedded biopsy samples of Barrett's mucosa without or with low-grade dysplastic change. 118 biopsy samples from 26 patients were taken during surveillance programs in time intervals ranging between 6 and 51 months.We found no significant increase in LOH events at least in a 51-month interval. In two patients, Barrett's adenocarcinoma was diagnosed 6 months after the first diagnosis of Barrett's mucosa. Six of 26 patients did not show LOH. The remaining patients exhibited a striking variation of LOH patterns and accumulations in biopsy samples during follow-up. From our microsatellite marker panel, we were not able to define a single surrogate marker that could serve as a potential biomarker, indicating an increased risk of progression to Barrett's adenocarcinoma. However, LOH combinations, especially APC/p16(INK4) or APC/p53, deserve attention as putative biomarkers in future studies.Our results raise important questions regarding the biological dynamics of mutations in Barrett's mucosa in addition to the influence of sampling, especially with regard to the number of biopsies taken from Barrett's mucosa. (C) 2008 Elsevier GmbH. All rights reserved.