Molecular characterisation and diagnosis of malignant mesothelioma

恶性间皮瘤（MM）是一种侵袭性的、与石棉有关的肿瘤，在全世界的发病率不断增加，估计每年造成约20，000人死亡。MM直到大约20-30年前才很罕见，但现在在澳大利亚，它与骨癌、肝癌、子宫颈癌、膀胱癌和卵巢癌一样是常见的死亡原因。虽然在大多数发达国家，石棉的使用已经下降到几乎为零，但由于疾病的潜伏期为30至40年，预计间皮瘤病例的高峰期要到2010年才会出现。MM是已知的最具侵袭性和使人衰弱的肿瘤之一，中位生存期为7-10个月，临床模式通常涉及大量疼痛和呼吸困难。间皮瘤治疗预防的进展不仅会对健康产生重大影响，而且可能产生非凡的经济影响。MM预计将在未来35-40年内使澳大利亚经济损失约50亿澳元的赔偿金。政府、保险公司和工业界将分担这一费用。因此，这种疾病的重要性超出了其实际发病率。在许多肿瘤类型中，越来越多的证据表明，对癌症的最佳诊断和治疗将是理解致癌基础的分子逻辑并相应地设计治疗和诊断的结果。我们将开展一个项目，使用最全面的微阵列可用于基因表达谱恶性间皮瘤。我们将使用我们获得的表达数据来实现三个目标。首先，我们将使用患者的结果信息来搜索其表达指示对治疗的反应的基因。其次，我们将搜索的数据，以确定候选分泌分子，这可能是有用的MM的早期检测。最后，我们将开发一种分子测定明确诊断MM从胸腔积液收集的细胞。

Malignant mesothelioma (MM) is an aggressive, asbestos-related tumour of increasing incidence throughout the world that is estimated to be cause approximately 20,000 deaths per annum . MM was rare until approximately 20-30 years ago but it is now more, or as, common a cause of death in Australia as cancers of the bone, liver, cervix, bladder and ovary. Although asbestos use has declined to virtually zero across most of the developed world, due to 30 to 40 year latency of the disease, the peak in cases of mesothelioma is not expected until 2010. MM is one of the most aggressive and debilitating tumours known, with a median survival of 7-10 months and a clinical pattern that usually involves substantial pain and dyspnea. Advances in therapy-prevention of mesothelioma will have not only have a major health impact, but potentially an extraordinary economic impact. MM is predicted to cost the Australian economy around $5 billion in compensation over the next 35-40 years. Government, insurance companies and industry will share that cost. The significance of this disease therefore extends beyond its actual incidence. There is growing evidence in many tumour types that the best diagnostics and treatments for cancer will come about as a result of understanding the molecular logic that underpins carcinogenesis, and designing therapies and diagnostics accordingly. We will carry out a project using the most comprehensive microarrays available to profile gene expression in malignant mesothelioma. We will use the expression data we obtain to fulfil three aims. Firstly, we will use patient outcome information to search for genes whose expression is indicative of response to therapy. Secondly, we will search the data to identify candidate secreted molecules which may be useful in the early detection of MM. Finally, we will develop a molecular assay to unequivocally diagnose MM from cells collected from pleural effusions.