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

(1)本研究采用比较基因组杂交（CGH）技术对34例食管鳞状细胞癌进行了分析。DNA拷贝数在3q（75%）、8 q23-qter（50%）、11 q13（44%）、5 p14-pter（25%）、20 q（25%）、7 q（22%）和2 p（19%）处增加，而在18 q（58%）、3 p（50%）、9 p（44%）、5 q14 -23（39%）、4 q（33%）、13 q（22%）和11 q22-qter（19%）。在11 q13、2 q12、7 q21、20q11.2检测到DNA扩增（高水平增益）。与临床病理结果比较，8 q23-qter（p<0.0005）、20 q（p <0.02）和11 q22（p <0.05）缺失与淋巴结转移密切相关。这些结果表明，淋巴结转移的诊断估计活检标本。由于在早期和晚期癌症中观察到3q和11 q13的增加以及18 q，3 p，9 p，5 q14 -23和4 q的丢失，这些被认为是与食管癌发生有关的遗传改变。(2)细胞系：我们用CGH分析了6个从人食管鳞癌中建立的细胞系，这6个细胞系共有3q、5 p、7 p、8 q、11 q、13 q、17 p、20 q和Xq的增加和4 q、9 q和18 q的丢失。3个细胞系在无胎血清条件下增殖时7 p12 -13、11 q14 -22和11 q22-qter增加，4p、8 p和11 p14-qter丢失，而12 p和20 p增加，3 p和5 q丢失仅见于其它细胞系。这些结果表明，细胞增殖特性与肿瘤细胞的遗传学改变有关，细胞系中观察到的遗传学改变与手术标本中观察到的遗传学改变一致。

(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.