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目的筛查声门上喉癌发生、发展及转移相关的异常染色体和重要基因. 方法应用比较基因组杂交(comparative genomic hybridization, CGH)分析喉声门上鳞状细胞癌(laryngeal squamous cell cancer, LSCC)癌组织和癌旁组织DNA拷贝数的差异.应用cDNA芯片结合聚类分析研究喉声门上癌癌旁组织、癌组织和转移淋巴组织中差异表达的基因.结果 CGH结果表明每例喉癌平均涉及12.9个染色体的异常,其中出现高频率扩增的染色体区集中在3q15-21 (14/18)、5p12-13 (11/18)、8q22-24 (6/18)、11q12-13 (8/18)、15q21-23 (7/18) and 18p11 (8/18),而高频率缺失的染色体区集中在1p13-21 (8/18)、3p21-23 (14/18)、5q21-22 (14/18)、9p12-pter (11/18) and 13q21-31 (8/18).聚类分析将表达差异的基因分为3组.表达差异在5倍以上的基因12个,在由癌旁至癌阶段、癌至转移阶段均存在表达异常的基因3个.这15个重要基因是喉癌新的相关基因,其中4个基因cytochrome C oxidase Ⅴa, PPBP, EPHX2 andPON1与喉癌相关性的研究未见报道,而且,SH3GL2位于高频率缺失的染色体区9p12-pter.结论我们发现的特异染色体区和重要基因将为喉癌发生、发展和转移的研究提供重要线索.

Objective With the objective of discovering novel putative chromosomal regions and special genes involved in the carcinogenesis, progression and metastasis of laryngeal squamous cell cancer (LSCC). Methods DNA copy profile of LSCC were obtained and analyzed by comparative genomic hybridization (CGH) and a computerized digital image analysis system. cDNA microarray of LSCC was performed and the profile was analyzed by Hierarchical clustering. Results CGH analysis showed average-12.9 gains and losses of chromosomes in LSCC. Relatively high frequencies of gains were found at 3q15-21 (14/18), 5p12-13 (11/18), 8q22-24 (6/18), 11q12-13 (8/18), 15q21-23 (7/18) and 18p11 (8/18), while those of losses at 1p13-21 (8/18), 3p21-23 (14/18), 5q21-22 (14/18), 9p12-pter (11/18) and 13q21-31 (8/18). Hierarchical clustering analysis showed that the differentially expressed genes were segregated into three groups. Three genes differentially expressed in processⅠ( normal tissue to cancer) and processⅡ(cancer to lymph node metastasis), and the Cy5/Cy3 ratios of twelve genes were either higher than 5.0 or lower than 0.2 in processⅠor processⅡ. The fifteen special genes were first reported possibly to be the relationships with LSCC. In particular, 4 genes of them, which were cytochrome C oxidase Ⅴa, PPBP,EPHX2 andPON1, were first reported to correlate with tumorigenesis.SH3GL2, which was one of the 15 special genes, was located at one of the special chromosome regions, 9p12-pter. Conclusion The important genes and special chromosomal aberrances might provide us a clue for further investigation of carcinogenesis, progression and metastasis in LSCC.