Comprehensive High-throughput Mapping of Cancer Genomes

描述(由申请人提供)：该项目旨在开发全面、快速和经济的方法来检测癌症中反复出现的染色体异常。该方法将允许在KBP分辨率水平上检测数百个小(&lt；1000细胞)样本中反复出现的染色体异常，包括由平衡重排引起的微小缺失和异常连接。这一开发项目采用了对大规模基因组测序和测绘至关重要的下一代技术和方法。为了使非基因组学专家的基础科学家和临床医生能够分析结果数据，这些方法将得到Genboree的支持，Genboree是在BCM人类基因组测序中心基因组测绘项目的背景下开发的交钥匙网络可访问的信息系统。反复重排具有生物学和临床重要性：1)它们被认为是癌症进展的致病事件，2)它们可以作为高度信息量的诊断和预后标记物，3)它们已经成为治疗的靶点。对多个转化细胞系和原发肿瘤样本的基因组进行高分辨率的综合图谱将揭示新的具有生物学和临床意义的复发性染色体异常。复发性染色体异常最常见于白血病、淋巴瘤和肉瘤。然而，最近的证据表明，癌症也包含生物上重要的高度重复的重排，我们的目标是使用所提出的方法来发现这一点。由于癌细胞重排的复杂结构和细胞群体的异质性，用目前的细胞遗传学方法只能部分检测到复发性重排。对高度重排的基因组的研究，如在乳腺癌和其他癌症中发现的基因组，将特别受益于分辨率的提高，而不是目前可用的技术。该项目将开发一种新技术，用于识别与乳腺癌和其他实体肿瘤的进展有关的基因异常。乳腺癌是女性中最常见的癌症。通过应用这项技术获得的关于特定基因异常的知识将使新的高度靶向癌症疗法的开发成为可能。

DESCRIPTION (provided by applicant): This project aims to develop comprehensive, rapid, and economical methods for detecting recurrent chromosomal aberrations in cancer. The methods will allow detection of recurrent chromosomal aberrations in hundreds of small (< 1000 cells) specimens at the Kbp level of resolution, including small deletions and aberrant joins induced by balanced rearrangements. This development project employs next-generation technologies and methodologies essential for large-scale genome sequencing and mapping .To enable analyses of resulting data by basic scientists and clinicians who are not experts in genomics, the methods will be supported by Genboree, a turnkey web- accessible informatic system developed in the context of genome mapping projects at the BCM Human Genome Sequencing Center. Recurrent rearrangements have both biological and clinical importance: 1) they have been implicated as causative events in cancer progression, 2) they can be used as highly informative diagnostic and prognostic markers, and 3) they have served as therapeutic targets. Comprehensive high-resolution mapping of genomes in multiple transformed cell lines and primary tumor samples will reveal novel biologically and clinically significant recurrent chromosomal aberrations. Recurrent chromosomal aberrations are best understood in leukemias, lymphomas, and sarcomas. However, recent evidence suggests that carcinomas also contain biologically important highly recurrent rearrangements, which we aim to discover using the proposed methods. Due to the more complex structure of rearrangements and heterogeneity of cell populations in carcinomas, recurrent rearrangements are only partially detectable using current cytogenetic methods. The study of highly rearranged genomes such as those found in breast cancer and other carcinomas will particularly benefit from an increase in resolution beyond currently available technologies. This project will develop a novel technology for identifying gene aberrations that are involved in the progression of breast cancer, the most common cancer among women, and in the progression of other solid tumors. The knowledge about specific gene aberrations gained through the application of the technology will enable development of novel highly targeted cancer therapies.