CHROMOSOMAL AND GENETIC ABERRATIONS RELATED TO THE DEVELOPMENT AND PROGRESSION OF ESOPHAGEAL CANCER

(1)手术标本。本研究对34例食管鳞状细胞癌进行比较基因组杂交（CGH）分析。DNA拷贝数在3q（75%）、8q23-qter（50%）、11q13（44%）、5p14-pter（25%）、20q（25%）、7q（22%）和2p（19%）处增加，在18q（58%）、3p（50%）、9p（44%）、5q14-23（39%）、4q（33%）、13q（22%）和11q22-qter（19%）处减少。在11q13、2q12、7q21、20q11.2处检测到DNA扩增（高增益）。这些基因变化与临床病理结果的比较显示，肿瘤淋巴结转移与8q23-qter的增加（p<0.0005）和20q的增加（p<0.02）以及11q22的减少（p<0.05）密切相关。这些结果表明淋巴结转移的诊断是在活检标本中估计的。由于3q和11q13的增加以及18q、3p、9p、5q14-23和4q的缺失在早期和晚期癌症中都可以观察到，这些被认为是与食道癌变有关的遗传改变。(2)细胞系。用CGH法对6株人食管鳞状细胞癌细胞系进行了分析。在这6个细胞系中，3q、5p、7p、8q、11q、13q、17p、20q和Xq的增益和4q、9q和18q的损失是共同的。7p12-13、11q14-22和11q22-qter的增加和4p、8p和11p14-qter的减少只在无胎血清培养基中增殖的3株细胞系中发现，而12p和20p的增加和3p和5q的减少只在其他需要胎血清生长的细胞系中发现。这些发现提示肿瘤细胞的增殖特征与肿瘤细胞的遗传变化有关。在细胞系中观察到的遗传变化与手术标本中的基因变化是一致的。

(1) Surgical specimens.In this project, 34 esophageal squamous cell carcinomas were analyzed by comparative benomic hybridization (CGH). DNA copy number increases were found at 3q (75%), 8q23-qter (50%), 11q13 (44%), 5p14-pter (25%), 20q (25%), 7q (22%), and 2p (19%), and decreases at 18q (58%), 3p (50%), 9p (44%), 5q14-23 (39%), 4q (33%), 13q (22%), and 11q22-qter (19%). DNA amplification (high-level gain) was detected at 11q13, 2q12, 7q21, 20q11.2. The comparison of these genetic changes with clinicopathological findings revealed that lymph node metastasis of cancer was closely associated with gains of 8q23-qter (p<0.0005) and 20q (p<0.02), and loss of 11q22 (p<0.05). These results suggest that diagnosis of lymph node metastasis is estimated in bioptic specimens. Since gains of 3q and 11q13, and losses of 18q, 3p, 9p, 5q14-23 and 4q were observed in both early and advanced cancers, these are considered to be genetic alterations involved in carcinogenesis of the esophagus.(2) Cell lines.We analyzed 6 cell lines established from human esophageal squamous cell carcinomas by CGH.Gains of 3q, 5p, 7p, 8q, 11q, 13q, 17p, 20q, and Xq, and losses of 4q, 9q, and 18q were common to these 6 cell lines. Gains of 7p12-13, 11q14-22, and 11q22-qter, and losses of 4p, 8p, and 11p14-qter were found exclusively in 3 cell lines which proliferale in medium without fetal serum, whereas gains of 12p and 20p, and losses of 3p and 5q were seen only in others which need fetal serum to grow. These findings suggest that characteristics of cell proliferation are related to genetic changes of tumor cells.Genetic changes seen in cell lines were compatible with those in surgical specimens.