Biological and clinical characterisation of human phosphatidylinositide 3-kinase mutations

人磷脂酰肌醇 3-激酶突变的生物学和临床特征

• 批准号: nhmrc : 400099
• 负责人: Prof Ian Campbell
• 金额: $ 36.93万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/biological-clinical-characterisation-kinase-mutations/99823
• 关键词: Biological; clinical; characterisation; human; phosphatidylinositide

Colorectal and breast cancers are the two most common registrable cancers in Australia and are second only to lung cancer in the total number of cancer deaths each year (4,678 and 2,612 deaths in 1997 for colorectal and breast, respectively). Ovarian cancer kills a further 740 women each year (Source: Cancer in Australia 1997, AIHW and AACR 2000). Thus, on average, one Australian dies of colorectal, breast or ovarian cancer every hour! Clearly, these are major diseases with a significant impact on our society. Unfortunately, though, we still do not understand the basic molecular and-or biochemical abnormalities that initiate and-or drive the development of these cancers. Our laboratory has recently reported a high frequency of mutation of the phosphoinositide 3-kinase (PI3K) gene PIK3CA in breast, colorectal and ovarian tumours. This work, funded by the NHMRC, has not only confirmed that PI3K is a bone fide human oncogene but also that mutations in the PI3K family of genes are one of the most common, and thus potentially one of the most important, genetic abnormalities in solid human tumours. In the current proposal, we aim to extend and complement our genetic studies by addressing the biological consequences and clinical significance of the mutations we have identified. This will provide crucial new insights into the biology of human tumourigenesis and further our understanding of the critical pathways and processes involved in the initiation and progression of human tumours. Such knowledge will help us to identify novel markers for diagnosis, prognosis and the early detection of cancer and enable a rational approach to the design of new anti-cancer therapies.

结肠直肠癌和乳腺癌是澳大利亚最常见的两种可登记的癌症，在每年癌症死亡总数中仅次于肺癌（1997年结肠直肠癌和乳腺癌分别有4，678人和2，612人死亡）。卵巢癌每年又造成740名妇女死亡（资料来源：澳大利亚癌症，1997年，卫生福利研究院和澳大利亚癌症研究所，2000年）。因此，平均每小时就有一名澳大利亚人死于结肠直肠癌、乳腺癌或卵巢癌！显然，这些都是对我们社会产生重大影响的重大疾病。然而不幸的是，我们仍然不了解引发和/或驱动这些癌症发展的基本分子和/或生化异常。我们的实验室最近报道了乳腺癌、结直肠癌和卵巢癌中磷酸肌醇3-激酶（PI 3 K）基因PIK 3CA的高频率突变。这项由NHMRC资助的工作不仅证实了PI 3 K是一种真正的人类癌基因，而且PI 3 K基因家族中的突变是最常见的基因之一，因此可能是人类实体肿瘤中最重要的遗传异常之一。在目前的提案中，我们的目标是通过解决我们已经确定的突变的生物学后果和临床意义来扩展和补充我们的遗传研究。这将为人类肿瘤发生的生物学提供重要的新见解，并进一步了解人类肿瘤发生和发展中所涉及的关键途径和过程。这些知识将帮助我们识别用于癌症诊断、预后和早期检测的新标志物，并使设计新的抗癌疗法的合理方法成为可能。