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食管鳞状细胞癌的比较基因组杂交:染色体畸变与疾病进展/预后的相关性

Comparative genomic hybridization of esophageal squamous cell carcinoma: correlations between chromosomal aberrations and disease progression/prognosis.

作者信息

Yen C C, Chen Y J, Chen J T, Hsia J Y, Chen P M, Liu J H, Fan F S, Chiou T J, Wang W S, Lin C H

机构信息

Division of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.

出版信息

Cancer. 2001 Dec 1;92(11):2769-77. doi: 10.1002/1097-0142(20011201)92:11<2769::aid-cncr10118>3.0.co;2-m.

Abstract

BACKGROUND

Esophageal carcinoma is a major cause of cancer-related deaths among males in Taiwan. However, to date, the genetic alterations that accompany this lethal disease are not understood.

METHODS

Chromosomal aberrations of 46 samples of esophageal squamous cell carcinoma (EC-SCC) were analyzed by comparative genomic hybridization (CGH), and their correlations with pathologic staging and prognosis were analyzed statistically.

RESULTS

In total, 321 gains and 252 losses were found in 46 tumor samples; thus, the average gains and losses per patient were 6.98 and 5.47, respectively. Frequent gain abnormalities were found on chromosome arms 1q, 2q, 3q, 5p, 7p, 7q, 8q, 11q, 12p, 12q, 14q, 17q, 20q, and Xq. Frequent deletions were found on chromosome arms 1p, 3p, 4p, 5q, 8p, 9p, 9q, 11q, 13q, 16p, 17p, 18q, 19p, and 19q. It was found that deletions of 4p and 13q12-q14 and gain of 5p were significantly correlated with pathologic staging. Losses of 8p22-pter and 9p also were found more frequently in patients with advanced disease. Gain of 8q24-qter was seen more frequently in patients with Grade 3 tumors. A univariate analysis found that pathologic staging; gains of 5p and 7q; and deletions of 4p, 9p, and 11q were significant prognostic factors. However, pathologic staging became the only significant factor in a multivariate analysis.

CONCLUSIONS

CGH not only revealed novel chromosomal aberrations in EC-SCC, but also found possible genotypic changes associated with disease progression. Despite all of the possible associations of chromosomal aberrations with disease progression, the most important prognostic factor for patients with EC-SCC was pathologic staging.

摘要

背景

在台湾地区,食管癌是男性癌症相关死亡的主要原因。然而,迄今为止,对于这种致命疾病所伴随的基因改变尚不清楚。

方法

采用比较基因组杂交(CGH)技术分析46例食管鳞状细胞癌(EC-SCC)样本的染色体畸变情况,并对其与病理分期及预后的相关性进行统计学分析。

结果

在46例肿瘤样本中共发现321处扩增和252处缺失;因此,每位患者的平均扩增和缺失数分别为6.98和5.47。常见的扩增异常出现在染色体臂1q、2q、3q、5p、7p、7q、8q、11q、12p、12q、14q、17q、20q和Xq上。常见的缺失出现在染色体臂1p、3p、4p、5q、8p、9p、9q、11q、13q、16p、17p、18q、19p和19q上。发现4p和13q12-q14的缺失以及5p的扩增与病理分期显著相关。8p22-pter和9p的缺失在晚期疾病患者中也更常见。8q24-qter的扩增在3级肿瘤患者中更常见。单因素分析发现,病理分期、5p和7q的扩增以及4p、9p和11q的缺失是显著的预后因素。然而,在多因素分析中,病理分期成为唯一的显著因素。

结论

CGH不仅揭示了EC-SCC中新型的染色体畸变,还发现了与疾病进展相关的可能的基因型变化。尽管染色体畸变与疾病进展存在所有可能的关联,但EC-SCC患者最重要的预后因素是病理分期。

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