Genetic analysis of long-term Barrett's esophagus epithelial cultures exhibiting cytogenetic and ploidy abnormalities
Genetic analysis of long-term Barrett's esophagus epithelial cultures exhibiting cytogenetic and ploidy abnormalities
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DOI：
10.1016/s0016-5085(98)70480-9
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发表时间：
1998-02-01
期刊：
影响因子：
29.4
通讯作者：
Rabinovitch, PS
中科院分区：
文献类型：
--
作者：
Palanca-Wessels, MC;Barrett, MT;Rabinovitch, PS
背景和目标：Barrett食管的癌症进展是通过体内记录的细胞周期和遗传异常的积累而发生的。为了更好地研究Barrett食管中的肿瘤演变，本研究的目的是从肿瘤前组织建立体外培养物。使用机械和酶促解离方法从内窥镜活检标本中启动巴雷特上皮培养物，结果：从39次实验中建立了4种长期培养物，所有培养物均含有细胞遗传学异常和流式细胞术4 N DNA含量升高的部分，检测到的分子遗传学异常包括：4例培养物中有4例存在9 p和/或CDKN 2/p16异常，3例培养物中存在17 p杂合性缺失和p53突变，1例培养物中存在5 q杂合性缺失。结论：这些培养物含有细胞周期和分子遗传异常，这些异常与先前记录的体内巴雷特食管癌症发展早期发生的异常密切相关。这些改变似乎也与体外成功生长相关。这些培养物可以提供一个癌前体外系统，用于测试巴雷特食管的潜在疗法，并检查在肿瘤进展中重要的病因因素和遗传中间体。
Background & Aims: Progression to cancer in Barrett's esophagus occurs through an accumulation of cell cycle and genetic abnormalities that have been documented in vivo, To better study neoplastic evolution in Barrett's esophagus, the aim of this study was to establish in vitro cultures from preneoplastic tissues, Methods: Mechanical and enzymatic dissociation methods were used to initiate Barrett's epithelial cultures from endoscopic biopsy specimens, and the cells were characterized using flow-cytometric, cytogenetic, and molecular genetic analyses, Results: Four long-term cultures were established from 39 attempts, All cultures contain cytogenetic abnormalities and elevated flow-cytometric 4N DNA content fractions, Molecular genetic abnormalities detected include the following: 9p and/or CDKN2/p16 abnormalities in 4 of 4 cultures, 17p loss of heterozygosity and p53 mutation in 3 of 4 cultures, and 5q loss of heterozygosity in 1 of 4 cultures, Inactivation of p53 was statistically associated with successful long-term culture. Conclusions: These cultures contain cell cycle and molecular genetic abnormalities that closely parallel those previously documented to occur early in cancer development in Barrett's esophagus in vivo, These alterations also appear to be associated with successful growth in vitro. The cultures may provide a premalignant in vitro system in which to test potential therapies for Barrett's esophagus as well as to examine etiologic factors and genetic intermediates important in neoplastic progression.