食管不典型增生和早期食管鳞癌全基因组的变化特征分析  

Analyzing the profile of chromosomal imbalances in esophageal atypical hyperplasia and early stage esophageal squamous cell carcinoma by 250K SNP array

作　　者：张旭[1] 朱志华[1] 林鹏[1] 杨弘[1] 傅剑华[1] 张兰军[1] 龙浩[1] 文静[1] 黄晓平[2] 方嬿[2] 戎铁华[1] 

机构地区：[1]中山大学肿瘤医院胸科,广州510060 [2]华南肿瘤学国家重点实验室

出　　处：《中华医学杂志》2008年第37期2636-2641,共6页National Medical Journal of China

基　　金：国家自然科学基金资助项目（30572103）;广东省自然科学基金资助项目（5300808）;广东省卫生厅基金资助项目（B2006067）

摘　　要：目的应用SNP芯片检测食管不典型增生和早期食管鳞癌全基因组的DNA拷贝数异常和杂合性缺失（LOH），探讨它们的变化特征。方法应用Affymetrix GeneChip Human Mapping 250K NspArray芯片检测1例原发性食管重度不典型增生和4例原发性早期食管鳞癌病变组织和配对正常食管组织的DNA拷贝数的变化和LOH。结果食管重度不典型增生只有极少数的DNA片段发生扩增，未发生缺失或LOH。早期食管鳞癌发生DNA扩增的染色体有1p、1q、2p、2q、3q、4q、5p、6p、6q、7q、8q、11p、11q、12p、12q、14q、17q、18p、19q、20q、22q和X；发生DNA缺失的染色体有1p、2q、3p、3q、4p、4q、8p、9p、9q、10q、11P、13q、16p、18q、19p、19q和22q；发生LOH的染色体有3q和9q。其中1p、19q、4q、11p等染色体发生扩增和3q、11p、2q、16p等染色体发生缺失罕见报道。结论食管重度不典型增生DNA的变异不明显；早期食管鳞癌DNA发生明显的扩增和缺失，但很少发生LOH。250K SNP芯片能够有效地检测食管不典型增生和早期食管鳞癌全基因组范围DNA拷贝数的变化及LOH，分辨率高，定位精确，这些结果为进一步定位筛选和克隆与早期食管鳞癌相关的基因提供了重要的理论信息。Objective To detect DNA copy number abnormality and LOH and explore the profile of chromosomal imbalances in esophageal atypical hyperplasia and early stage esophageal squamous cell carcinoma using SNP array. Methods The DNA copy number abnormality and LOH in pathological change esophageal tissue and matched normal esophageal tissue of one case of primary esophageal high atypical hyperplasia and four cases of primary early stage esophageal squamous cell carcinoma were detected by using Mfymetrix GeneChip Human Mapping 250K NspArray. Results Amplification was found in a few DNA fragment and no deletion or LOH was found in esophageal high atypical hyperplasia. In early stage esophageal squamous cell carcinoma , DNA amplification occurred in 1p, 1q, 2p, 2q, 3q, 4q, 5p, 6p, 6q, 7q, 8q, 11p, 11q, 12p, 12q, 14q, 17q, 18p, 19q, 20q, 22q and X chromosome. DNA deletion occurred in 1p, 2q, 3p, 3q, 4p, 4q, 8p, 9p, 9q, 10q, lip, 13q, 16p, 18q, 19p, 19q and 22q chromosome. LOH occurred in 3q and 9q chromosome. The amplification in 1p, 19q, 4q, 11 p chromosome and the deletion in 3q, 11 p, 2q, 16p chromosome were rarely reported. Conclusion DNA abnormality was rare in esophageal high atypical hyperplasia. The obvious amplification and deletion in DNA have been found in early stage esophageal squamous cell carcinoma, but LOH was rarely found. 250K SNP array could effectively detect DNA copy number change and LOH in whole-wide genes in esophageal atypical hyperplasia and early stage esophageal squamous cell carcinoma with high distinguishability and precise location. The results would provide important academic information for detection and location of related genes in early stage esophageal squamous cell carcinoma.

关 键 词：食管不典型增生 食管癌 SNP芯片 DNA拷贝数 LOH 

分 类 号：R686[医药卫生—骨科学]