Genetic Modifiers of Intitiation and Progression of Mamm

我们实验室的最新进展是显著的。在过去的一年里，我们发表了第一个关于体质多态对转移的影响的研究结果。我们证明，SIpa1基因中的单一氨基酸多态可以将小鼠乳腺肿瘤的转移能力调节多达10倍。此外，我们利用初步的人类流行病学研究证明，该基因的人类同源基因SIPA1的多态与人类乳腺癌的淋巴转移状态有关。这些发现是第一个发表的例子，表明遗传而不是肿瘤内的突变在人类癌症的进展中起着主要作用。这些结果也开启了从血液等正常组织预测那些有转移疾病风险的患者的可能性。我们的发现证实了这一假设，即基于蛋白质表达谱，可以使用基因表达谱来预测我们的小鼠模型系统中的哪些动物将发生肺转移。

Recent progress in our laborabory has been significant. During the past year we published the results of our first study of the effect of constitutional polymorphism influencing metastasis. We demonstrated that a single amino acid polymorphism in the gene Sipa1 could modulate the metastatic capacity of mouse mammary tumors by as much as ten-fold. Furthermore we demonstrated, using pilot human epidemiology studies, that polymorphisms in the human ortholog of this gene, SIPA1, were associated with lymphnode status in human breast cancer. These findings were the first published example that genetic inheritance rather that mutation within tumors, plays a major role in progression of human cancer. These results also open up the possibility that it is possible to predicted those patients at risk of metastatic disease prospectively, from normal tissues such as blood. This hypothesis was confirmed by our finding that it was possible, using gene expression profiling, to predicted which animals in our mouse model system were going to develop lung metastasis, based on protein expression profiles.