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8号染色体长臂增加:可切除胰腺癌的潜在预后标志物?

Gain of chromosome 8q: a potential prognostic marker in resectable adenocarcinoma of the pancreas?

作者信息

Schleicher Christina, Poremba Christopher, Wolters Heiner, Schäfer Karl-Ludwig, Senninger Norbert, Colombo-Benkmann Mario

机构信息

Department of General Surgery, University of Muenster, Waldeyerstrasse 1, 48149 Muenster, Germany.

出版信息

Ann Surg Oncol. 2007 Apr;14(4):1327-35. doi: 10.1245/s10434-006-9113-x. Epub 2007 Jan 18.

Abstract

BACKGROUND

The objective of this study was to identify genomic alterations in resectable pancreatic cancer (PCA). Chromosomal imbalances were correlated with histopathological and clinical data to verify their prognostic significance.

METHODS

Specimens of 33 PCA were investigated by comparative genomic hybridization. Microdissection was used for separation of PCA from the normal cells before isolation of DNA; nick-end labeling and hybridization were performed according to standard protocols. Aberrations were correlated with staging and grading using log-rank test and Cox regression. Survival rates were plotted using the Kaplan-Meier method.

RESULTS

Twenty-eight (85%) PCA showed aberrations. Gains of chromosomal material were most frequently identified on 8q (42%), 13q (30%), 18p (21%), and 3q (18%). Genetic losses were frequently detected on 1p (45%), 22 (42%), 19 (36%), 17p (27%), 18q and 8p (15% each), and 3p (12%). Losses of 8p (n = 5) and 3p (n = 4) were only detected in stages III and IV (P < 0.05). Median survival time of all patients was 13 months. Median survival time of patients with aberration of 8q (n = 14) was 8.5 months compared to 16 months in patients without gain of 8q (n = 19; P = 0.029).

CONCLUSIONS

The chromosomal regions containing genetic alterations represent potential loci for new target genes in PCA. The significant correlation of gain of chromosome 8q with short survival time suggests that 8q may be a new marker to assess prognosis and malignant potential of resected PCA in the individual patient, thereby helping to identify patients at risk for recurrence that might profit from adjuvant therapy.

摘要

背景

本研究的目的是识别可切除胰腺癌(PCA)中的基因组改变。将染色体失衡与组织病理学和临床数据相关联,以验证其预后意义。

方法

采用比较基因组杂交技术对33例PCA标本进行研究。在分离DNA之前,使用显微切割技术将PCA与正常细胞分离;缺口末端标记和杂交按照标准方案进行。使用对数秩检验和Cox回归分析畸变与分期和分级的相关性。采用Kaplan-Meier法绘制生存率曲线。

结果

28例(85%)PCA显示有畸变。染色体物质的增加最常见于8q(42%)、13q(30%)、18p(21%)和3q(18%)。基因缺失常见于1p(45%)、22(42%)、19(36%)、17p(27%)、18q和8p(各15%)以及3p(12%)。8p(n = 5)和3p(n = 4)的缺失仅在III期和IV期检测到(P < 0.05)。所有患者的中位生存时间为13个月。8q有畸变的患者(n = 14)的中位生存时间为8.5个月,而无8q增加的患者(n = 19)为16个月(P = 0.029)。

结论

含有基因改变的染色体区域代表PCA中新靶基因的潜在位点。8号染色体q臂增加与短生存时间的显著相关性表明,8q可能是评估个体患者可切除PCA预后和恶性潜能的新标志物,从而有助于识别可能从辅助治疗中获益的复发风险患者。

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