Legoffic Aude, Calvo Ezequiel Luis, Barthet Marc, Delpero Jean-Robert, Dagorn Jean Charles, Iovanna Juan Lucio
INSERM U.624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, Marseille, France.
Pancreatology. 2009;9(3):267-72. doi: 10.1159/000212092. Epub 2009 Apr 29.
Genomic alterations present in pancreatic adenocarcinoma have been described only partially. In addition, the relations between these alterations and the aggressiveness of the phenotype remain unknown.
Genomic DNA and total RNA from 5 pancreatic cell lines, of which 2 have an aggressive phenotype and are gemcitabine-resistant (Mia-Paca2 and Panc-1), and 3 less aggressive and gemcitabine-sensitive (Capan-1, Capan-2 and BxPC3), have been purified. DNA abnormalities have been analyzed using an ultra-high-resolution CGH array and mRNA expression was studied with an Affymetrix GeneChip expression array.
We identified 573 amplified and 30 deleted genes common to all 5 cell lines. Some of them have already been described, whereas other genes, implicated in signal transduction, apoptosis, cell cycle or cell migration, are described for the first time as being related to this cancer. Comparison of genomic abnormalities between the 2 most aggressive and the 3 less aggressive cell lines led to the identification of 368 genes specifically amplified in the aggressive cell lines. However, no specific gene deletion seems to be associated with the aggressive phenotype.
Using a high-resolution approach, we could precisely describe the genomic alterations associated with pancreatic adenocarcinoma and determine those associated with an aggressive phenotype.
胰腺腺癌中存在的基因组改变仅得到部分描述。此外，这些改变与表型侵袭性之间的关系仍不清楚。
已从5种胰腺细胞系中纯化出基因组DNA和总RNA，其中2种具有侵袭性表型且对吉西他滨耐药（Mia-Paca2和Panc-1），3种侵袭性较弱且对吉西他滨敏感（Capan-1、Capan-2和BxPC3）。使用超高分辨率比较基因组杂交阵列分析DNA异常情况，并使用Affymetrix基因芯片表达阵列研究mRNA表达。
我们鉴定出了所有5种细胞系共有的573个扩增基因和30个缺失基因。其中一些基因已被描述过，而其他与信号转导、凋亡、细胞周期或细胞迁移有关的基因则首次被描述与这种癌症相关。比较2种侵袭性最强和3种侵袭性较弱的细胞系之间的基因组异常情况，发现了368个在侵袭性细胞系中特异性扩增的基因。然而，似乎没有特定的基因缺失与侵袭性表型相关。
采用高分辨率方法，我们能够精确描述与胰腺腺癌相关的基因组改变，并确定与侵袭性表型相关的改变。
