High resolution chromosome 3p, 8p, 9q and 22q allelotyping analysis in the pathogenesis of gallbladder carcinoma.
High resolution chromosome 3p, 8p, 9q and 22q allelotyping analysis in the pathogenesis of gallbladder carcinoma.
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DOI：
10.1038/sj.bjc.6600490
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发表时间：
2002-08-12
影响因子：
8.8
通讯作者：
Gazdar, AF
中科院分区：
文献类型：
--
作者：
Wistube, II;Maitra, A;Carrasco, R;Tang, M;Troncoso, P;Minna, JD;Gazdar, AF
我们最近对胆囊癌进行全基因组等位基因分型分析，确定 3p、8p、9q 和 22q 是经常发生杂合性丢失的染色体区域。本研究的目的是更精确地确定胆囊癌中涉及这些染色体的频繁等位基因丢失区域的存在和位置。使用跨越染色体 3p (n=26)、8p (n=14)、9q (n=29) 和 22q (n=12) 区域的 81 个微卫星标记，对 24 个胆囊癌的显微解剖组织进行基于 PCR 的杂合性丢失分析。我们还通过使用 17 个微卫星标记检查 45 个伴随胆囊癌的显微解剖正常和发育异常的胆囊上皮，研究了这些等位基因丢失在胆囊癌发病机制中的作用。胆囊癌中 3p (100%)、8p (100%)、9q (88%) 和 22q (92%) 位点杂合性丢失的总体频率非常高，我们确定了肿瘤中 13 个经常发生杂合性丢失的不同区域。在正常和发育不良的胆囊上皮中经常检测到等位基因丢失。随着组织病理学变化严重程度的增加，杂合性总体丢失频率逐渐增加。等位基因丢失不是随机的并且遵循序列。这项研究精炼了胆囊癌中经常发生等位基因丢失的几个不同的染色体 3p、8p、9q 和 22q 区域，这将有助于确定参与胆囊癌发病机制的抑癌基因的位置。英国癌症杂志 (2002) 87, 432–440。 doi:10.1038/sj.bjc.6600490 www.bjcancer.com © 2002 英国癌症研究中心
Our recent genome-wide allelotyping analysis of gallbladder carcinoma identified 3p, 8p, 9q and 22q as chromosomal regions with frequent loss of heterozygosity. The present study was undertaken to more precisely identify the presence and location of regions of frequent allele loss involving those chromosomes in gallbladder carcinoma. Microdissected tissue from 24 gallbladder carcinoma were analysed for PCR-based loss of heterozygosity using 81 microsatellite markers spanning chromosome 3p (n=26), 8p (n=14), 9q (n=29) and 22q (n=12) regions. We also studied the role of those allele losses in gallbladder carcinoma pathogenesis by examining 45 microdissected normal and dysplastic gallbladder epithelia accompanying gallbladder carcinoma, using 17 microsatellite markers. Overall frequencies of loss of heterozygosity at 3p (100%), 8p (100%), 9q (88%), and 22q (92%) sites were very high in gallbladder carcinoma, and we identified 13 distinct regions undergoing frequent loss of heterozygosity in tumours. Allele losses were frequently detected in normal and dysplastic gallbladder epithelia. There was a progressive increase of the overall loss of heterozygosity frequency with increasing severity of histopathological changes. Allele losses were not random and followed a sequence. This study refines several distinct chromosome 3p, 8p, 9q and 22q regions undergoing frequent allele loss in gallbladder carcinoma that will aid in the positional identification of tumour suppressor genes involved in gallbladder carcinoma pathogenesis. British Journal of Cancer (2002) 87, 432–440. doi:10.1038/sj.bjc.6600490 www.bjcancer.com © 2002 Cancer Research UK
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