应用原位杂交技术比较肺腺癌和肺鳞癌的内在分子机制

Multicolor fluorescence in situ hybridization and comparative genomic hybridization reveals molecular events in lung adenocarcinomas and squamous cell lung carcinomas

目的分析肺腺癌及肺鳞癌肿瘤中染色体异常变化和基因组的改变。探讨肺腺癌及肺鳞癌细胞遗传物质的改变,揭示这两种NSCLC主要亚型发生发展的内在本质及其与临床特征之间的关系。方法应用M-FISH技术,检测肺腺癌及肺鳞癌细胞株各1株,观察其染色体数目及结构畸变情况,应用CGH技术对80例肺腺癌组织80例肺鳞癌组织中所提取的全基因组DNA进行检测,比较这两种类型的NSCLC全基因组的变化。结果M-FISH结果显示肺腺癌及肺鳞癌细胞中存在许多复杂的染色体重排,其中5、6、11、12、17号染色体最频繁参于染色体间的易位。CGH发现,在160例肺癌标本基因组中,最常见的扩增区域足1 q,2 p,3 q,5 p,5 q,7 p,8 q,11 q,12 q,14 q,16 p,17 p.19 p,20 q,21 q,22 q。最常见的缺失区域是2 q.3 p,4 p,5 q,7 q,8 p,9 p.13 q,14 q,17 p。在肺腺癌中最常见的扩增位点足16p13,阳性率达50%.而肺鳞癌中最常见的扩增位点是17q21(45%),并且这两个位点的变异在肺腺癌和肺鳞癌之间有着显著性的差异(P<0.05)。结论M- FISH和CGH技术是研究肺癌基因组变化的强有力的工具,本实验中发现的基因改变町能代表了与肺腺癌及肺鳞癌特有的病理,诊断相关和候选基因。

Objective To analyze the chromosomal aberrations and alterations of the genomes in lung adenocarcinomas and squamous cell lung carcinomas and thus to reveal the nature of the development of the two specific pathological subtypes of NSCLC and their＇s relationship with clinography. Methods We have used the molecular cytogenetic techniques of multicolor fluorescence in situ hybridization （M-FISH） and comparative genomic hybridization （CGH） to analyze two established lung cancer cell lines （A549, H520）, 80 primary lung adenocarcinoma samples and 80 squamous cell lung carcinoma samples in order to identify common chromosomal aberrations. Results M-FISH revealed numerous complex chromosomal rearrangements. Chromosomes 5, 6, 11, 12, 17 were most frequently involved in interchromosomal translocations. CC-H revealed regions on 1 q, 2 p, 3 q, 5 p, 5 q, 7p, 8 q, 11 q, 12 q, 14q, 16 p, 17p, 19q, 20 q, 21 qand 22 q to be commonly overrepresented and regions on 2 q, 3 p, 4 p, 5 q, 7 q, 8 p, 9 p, 13 q, 14 q, 17 p to be un- derrepresented. In lung adenocarcinomas the most common gains were found in 16p13 （50%）, while in squamous cell lung carcinomas the common gains were found in 17q21（45% ） and these alterations were observed to be associated with their specific pathological subtype. Conclusions In conclusion, the present study contributes to the molecular biological characterization in lung adeno- carcinomas and squamous cell lung carcinomas and through evaluation of molecular events to the recently emergent focus on novel markers for lung cancer treatment.