胃癌及癌前病变组织染色体7q31.1杂合性缺失的意义
Significance of Loss of Heterozygosity at Chromosome 7q31.1 in Human Gastric Carcinoma and Precancerous Lesions
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摘要: 目的 检测胃癌及不典型增生细胞染色体7q31.1区域的杂合性缺失（LOH），绘制胃癌及癌前病变7q31.1区域等位基因缺失图谱，确定其常见最小缺失区域，探索胃黏膜上皮癌变过程不同阶段的分子遗传学改变。方法 在胃癌及胃黏膜组织石蜡切片上行显微切割，获得胃癌及胃黏膜上皮不典型增生细胞。用高密度微卫星标志结合PCR技术检测胃癌及癌前病变细胞染色体7q31.1杂合性缺失，绘制胃癌及癌前病变染色体7q31.1等位基因的缺失图谱。结果 发现胃癌染色体7q31.1至少有一个位点存在杂合性缺失的21例，占70.0%（21/30）；D7S2459、D7S523、D7S2502、D7S486、D7S480、D7S650、D7S2486各位点杂合性缺失频率分别为10.0%、6.7%、23.3%、43.3%、26.7%、26.7%、20.0%；缺失图谱分析显示胃癌常见最小缺失区域位于D7S2502~D7S480之间。在胃黏膜不典型增生组织中，至少一个位点等位基因缺失的11例，占36.7%（11/30），其中缺失频率最高的微卫星位点是D7S480为23.3%(7/30)；不同程度胃黏膜不典型增生患者中染色体7q31.1 LOH阳性率比较差别有统计学意义（P<0.01）。结论 胃癌染色体7q31.1常见最小缺失区域在D7S2502~D7S480之间，在D7S486附近可能存在与胃癌相关的抑癌基因。在胃黏膜癌前病变阶段（不典型增生）可检测出染色体7q31.1区域的杂合性缺失，7q31.1 LOH可能是胃癌发生极早期的分子事件之一。Abstract: Objective To analyze loss of heterozygosity (LOH) at chromosome 7q31.1 in human gastric carcinomas and precancerous lesions by microdissection，to construct allelic loss mappings and define the minimally lost regions (MLR) at chromosome 7q31.1，further to explore the molecular genetic alteration during the malignant progression of human gastric mucosa. Methods The gastric carcinoma and atypical hyperplasia lesions cells were microdissected from paraffin sections.Seven high dense microsatellite markers were used，combined with polymerase chain reaction (PCR)，to detect the frequencies of LOH of every selected microsatellite site at chromosome 7q31.1 in gastric carcinoma and precancerous lesions，then to map detailed alleic losses and define the minimally lost regions on chromosome 7q31.1. Results requency of LOH at chromosome 7q31.1 in gastric carcinoma tissues achieved 70% (21/30).Seven microsatellite markers' frequencies of LOH in loci D7S2459，D7S523，D7S2502，D7S486，D7S480，D7S650 and D7S2486 were 10.0%，6.7%，23.3%，43.3%，26.7%，26.7% and 20.0%，respectively.Through analyzing allelic loss mapping on chromosome 7q31.1，we have found that the MLR was between D7S2502 and D7S480.Additionally，the 7q31.1 LOH was confirmed to be existed in the precancerous lesions of human gastric mucosa，but the frequency of LOH was lower.In the atypical hyperplasia of gastric mucosa，frequency of LOH reached 36.7% (11/30)，and the microsatellite marker with the highest loss frequency was D7S480 (23.3%，7/30).Frequencies of 7q31.1 LOH were significantly different with different degrees of atypical hyperplasia of gastric mucosa (P<0.01). Conclusion The MLR at chromosome 7q31.1 in gastric carcinoma is at the region from D7S2502 to D7S480，which suggests that the region probably harbors a candidate TSG associated with human gastric carcinoma.Gastric precancerous lesionsexists allelic loss at 7q31.1，which is one of the molecular incidences happened early during the development of gastric carcinoma.
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