BAC clones related to prognosis in patients with esophageal squamous carcinoma: An array comparative genomic hybridization study

BAC clones related to prognosis in patients with esophageal squamous carcinoma: An array comparative genomic hybridization study
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DOI:
10.1634/theoncologist.12-4-406
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发表时间:
2007-01-01
期刊:
影响因子:
5.8
通讯作者:
Hirano, Takashi
Hirano, Takashi
中科院分区:
医学2区
文献类型:
--
作者:
Hirasaki, Shigeo;Noguchi, Tsuyoshi;Hirano, Takashi

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目的.食管癌患者预后差。为了确定与患者预后不良相关的基因组改变,我们使用基于阵列的比较基因组杂交(aCGH)分析了食管鳞状细胞癌(ESC)的全DNA拷贝数谱。本文对21例手术切除和2例活检的食管鳞癌进行了研究。将每个样品激光显微切割以获得纯癌细胞群。提取的DNA用aCGH分析。最具代表性的改变之一是先前报道的11q13.3扩增。此外,还发现了一些新的变异,如16p13.3的缺失。在手术后5年以上重新评估的19名患者中,9名仍然活着,10名死于疾病复发。当比较存活组和死亡组的aCGH谱时,在4,030个细菌人工染色体(BAC)克隆中的68个中识别出显著差异。这些克隆中几乎有一半存在于4 q、13 q、20 q和Xq的9个限制区。对于这68个BAC克隆中的22个,当比较特定克隆中有改变的患者与没有改变的患者时,使用对数秩检验,Kaplan-Meier生存曲线也有显著差异。食管鳞癌的aCGH研究清楚地鉴定了与患者预后相关的BAC克隆。这些克隆使我们有机会确定与癌症进展相关的特定基因。
Purpose. The prognosis of patients with esophageal carcinoma is poor. To identify genomic alterations associated with poor patient prognosis, we analyzed whole DNA copy number profiles of esophageal squamous carcinomas (ESCs) using array-based comparative genomic hybridization (aCGH).Materials and Methods. Twenty-one operated and two biopsied cases of esophageal squamous cancer were examined for study. Each sample was laser microdissected to obtain pure cancer cell populations. The extracted DNA was analyzed using aCGH.Results. One of the most representative alterations was a previously reported amplification at 11q13.3. In addition, some novel alterations, such as deletion of 16p13.3, were identified. Of the 19 patients who were reassessed more than 5 years after the operation, nine were still living and 10 had died from disease recurrence. When aCGH profiles from the surviving group and the deceased group were compared, significant differences were recognized in 68 of 4,030 bacterial artificial chromosome (BAC) clones. Almost half of these clones were present at nine limiting regions in 4q, 13q, 20q, and Xq. For 22 of these 68 BAC clones, there also was a significant difference in the Kaplan-Meier survival curve, using the log-rank test, when comparing patients who had an alteration in a particular clone with those who did not.Conclusions. aCGH study of esophageal squamous cancer clearly identified BAC clones that are related to the prognosis of patients. These clones give us the opportunity to determine specific genes that are associated with cancer progression.