Extending and Interpreting Molecular Portraits of Cancer

描述（由申请人提供）：该项目旨在通过更好地了解癌症生物学，改进癌症分类和诊断，以及确定新的分子靶点和治疗策略，改善癌症患者的诊断和治疗。该多学科项目强调利用系统的、高度并行的方法来研究人类癌症的分子特征，特别是利用DNA微阵列和组织微阵列来分析基因和蛋白质的表达模式。核心假设是，癌症之间或癌症与正常细胞之间的任何临床重要差异，都将伴随着基因表达程序的相应差异。该计划的研究项目包括：(1)旨在识别和表征癌症组织微环境中的细胞及其相互作用的研究；细胞对癌症重要分子信号反应的系统研究；(2)前列腺癌的研究，旨在了解在以往工作中发现的三种不同的前列腺癌分子亚型的临床意义和生物学基础，将基因表达模式与染色体改变联系起来，并开发和评估新的预后标志物；(3)研究小型早期乳腺癌的整体基因表达和分子多样性，并对基于基因表达的预后标准在预测这些早期癌症临床病程中的作用进行关键评估；(4)对软组织肉瘤的基因表达模式进行大规模的系统研究，旨在为这些癌症的诊断和治疗开发新的分子标记，并提高我们对作为癌症共同特征的间质增殖的理解。该计划由一个行政核心（core C）支持，该核心将支持、组织和监督项目，以及两个研究核心——DNA微阵列信息学和生物统计学核心（core a），该核心将支持微阵列数据库，用于归档、分析和公开分发该项目数据，并为数据分析提供专家咨询和支持；组织微阵列核心（core B）将生产和提供组织微阵列，支持免疫染色和原位杂交，支持组织病理学解释，以及自动图像分析和图像数据库支持。

DESCRIPTION (provided by applicant):This program project seeks to improve the diagnosis and treatment of patients with cancer through a better understanding of cancer biology, improvements in cancer classification and diagnosis, and identification of new molecular targets and strategies for treatment. The multidisciplinary program emphasizes exploits systematic, highly parallel approaches to the molecular characterization of human cancer, particularly the use of DNA microarrays and tissue microarrays to profile gene and protein expression patterns. The central hypothesis is that any clinically important differences among cancers, or between cancers and their normal cellular counterparts, will be accompanied by a corresponding difference in gene expression programs. The research projects in this program include (1) a study aimed at identifying and characterizing the cells in the microenvironment of cancer tissues and their interactions, and; a systematic study of the cellular responses to molecular signals important in cancer; (2) a study of prostate cancer aimed at understanding the clinical implications and the biological basis of three distinct molecular subtypes of prostate cancer discovered in previous work, relating patterns of gene expression to chromosomal alterations, and developing and evaluating new prognostic markers; (3) a study of global gene expression and molecular diversity, in small, early stage breast cancers and a critical evaluation of the performance of gene-expression based prognostic criteria in predicting the clinical course of these early cancers; and (4) a large systematic investigation of the gene expression patterns in soft-tissue sarcomas, aimed at development of new molecular markers for diagnosis and new molecular targets for therapy of these cancers, and at improving our understanding of the stromal proliferation that is a common features of carcinomas. The program is supported by an administrative core (Core C) that will support, organize and provide supervision of the projects, and two research cores - a DNA microarray informatics and biostatistics core (Core A) that will support a microarray database for archiving, analysis and public distribution of data from this project and provide expert consultation and support for data analysis; and a tissue microarray core (Core B) that will produce and provide tissue microarrays, support for immunostaining and in situ hybridization, support for histopathological interpretation, and automated image analysis and image database support.