Karhu Ritva, Mahlamäki Eija, Kallioniemi Anne
Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland.
Genes Chromosomes Cancer. 2006 Aug;45(8):721-30. doi: 10.1002/gcc.20337.
Pancreatic adenocarcinoma is the fifth leading cause of cancer death with a 5-year survival rate of less than 5%. Although the role of a few known oncogenes and tumor suppressor genes in the development of pancreatic cancer is fairly well established, it is obvious that the majority of genetic changes responsible for the initiation and progression of this disease are still unknown. In this review, the authors will discuss the results from various genome-wide screening efforts, from traditional chromosome analyses to modern DNA microarray studies, which have provided an enormous amount of information on genetic alterations in pancreatic adenocarcinoma. Exciting findings have emerged from these studies, highlighting multiple potential chromosomal regions that may harbor novel cancer genes involved in the molecular pathogenesis of this lethal disorder. These findings complete the picture of pancreatic adenocarcinoma as a genetically highly complex and heterogeneous tumor type with an ongoing instability process. In addition, the precisely localized copy number changes offer a valuable starting point for further studies required to identify the genes involved and to characterize their potential functional role in the development and progression of pancreatic adenocarcinoma.
胰腺腺癌是癌症死亡的第五大主要原因,其5年生存率低于5%。尽管少数已知致癌基因和肿瘤抑制基因在胰腺癌发展中的作用已相当明确,但显然,导致这种疾病发生和进展的大多数基因变化仍不为人知。在这篇综述中,作者将讨论从传统染色体分析到现代DNA微阵列研究等各种全基因组筛查工作的结果,这些研究提供了关于胰腺腺癌基因改变的大量信息。这些研究已出现了令人兴奋的发现,突出了多个潜在的染色体区域,这些区域可能含有参与这种致命疾病分子发病机制的新型癌症基因。这些发现完善了胰腺腺癌作为一种基因高度复杂且异质性肿瘤类型以及一个持续不稳定过程的全貌。此外,精确定位的拷贝数变化为进一步研究提供了有价值的起点,这些研究需要确定相关基因并表征它们在胰腺腺癌发生和发展中的潜在功能作用。