An Assay System for Cancer Gene Discovery

描述(由申请人提供)：该项目的目标是开发一种创新的、高效的检测癌症中可能具有重要功能的基因的方法。检测这类基因面临许多挑战，包括癌症基因组的广泛突变和重排；可能出错的各种分子机制，导致癌症之间的广泛分子差异；以及癌症样本的异质性，这往往包括正常和异常细胞类型的混合。我们检测致癌基因的策略是应用微阵列概念来实现高通量全基因组筛选方法，这将有助于克服由于分子和细胞异质性造成的一些挑战。在项目的第一阶段，我们打算开发一个简单的模型系统，通过构建质粒克隆和使用针对少数基因的合成寡核苷酸来进行测试开发。在第二阶段，我们将扩大检测系统，以包括一大组基因，我们将使用实际的癌症样本和对照来验证检测系统。我们预计，一旦开发出来，我们的方法将允许以高分辨率、快速、可靠和成本效益的方式对许多样品进行筛选。我们的方法可能使发现在癌症中发挥重要作用的新基因成为可能。一些有助于将正常细胞转化为癌症细胞的基因已被证明是开发更有效的抗癌药物的良好靶点。然而，关于这些基因和它们的作用机制仍有很多有待发现的地方。这项提议旨在开发一种强大而有效的新方法来寻找重要的癌症基因，这可能会导致对这种疾病的更好了解，并改进测试和治疗。

DESCRIPTION (provided by applicant): The aim of this project is to develop an innovative, highly efficient assay for detecting genes that may be functionally important in cancer. There are a number of challenges to detecting such genes, including the extensive mutation and rearrangement of the cancer genome; the variety of molecular mechanisms which can go awry, leading to extensive molecular variation between cancers; and the heterogeneity of cancer samples, which tend to include a mixture of cell types, both normal and abnormal. Our strategy for detecting cancer causing genes is to apply microarray concepts to enable a high-throughput genome-wide screening approach that will help overcome some of the challenges due to molecular and cellular heterogeneity. In the first phase of the project, we intend to develop a simple model system for assay development by constructing plasmid clones and using synthetic oligonucleotides specific for a small number of genes. In Phase II, we will expand the assay system to include a large set of genes, and we will validate the assay system using actual cancer samples and controls. We expect that, once developed, our approach will allow many samples to be screened at a high resolution, rapidly, reliably and cost- effectively. Our approach may enable the discovery of new genes that play an important role in cancer. Some genes that help transform normal cells into cancerous ones have proven to be good targets for the development of more effective cancer drugs. However, much remains to be discovered about such genes and the mechanisms by which they act. This proposal is aimed at developing a powerful and efficient new way to find important cancer genes, which may lead to a better understanding of the disease and improved tests and treatments.