声门上喉癌的染色体异常和重要相关基因的研究(英文)  

Average-12.9 chromosome imbalances coupling with 15 differential expression genes possibly involved in the carcinogenesis, progression and metastasis of supraglottic laryngeal squamous cell cancer

作　　者：富伟能[1] 尚超[1] 黄带发[1] 徐振明[2] 孙兴和[2] 孙开来[1] 

机构地区：[1]中国医科大学医学遗传学教研室,沈阳110001 [2]中国人民解放军第463医院耳鼻喉科

出　　处：《中华医学遗传学杂志》2006年第1期7-11,共5页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(30171008);国家863计划项目子课题(2002BA711A08-18)~~

摘　　要：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 ge-nomic 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)and18p11(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)and13q21-31(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 oxidaseⅤa,PPBP,EPHX2and PON1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 genomie hybridization （CGH） and a computerized digital image analysis system, eDNA mieroarray 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 18p22 （8/18）, while those of losses at lp13-21 （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 process Ⅰ （ normal tissue to cancer） and process Ⅱ （ 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 process Ⅰ or process Ⅱ. The fifteen special genes were first reported possibly to be the relationships with LSCC. In particular, 4 genes of them, which were eytochrome C oxidase V a, PPBP, EPHX2 and PON1, 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. Condusion The important genes and special chromosomal aberrances might provide us a clue for further investigation of carcinogenesis, progression and metastasis in LSCC.

关 键 词：比较基因组杂交 CDNA芯片 喉鳞状细胞癌 癌发生 

分 类 号：R739.65[医药卫生—肿瘤] R596.1[医药卫生—临床医学]