Extending and Interpreting Molecular Portraits of Cancer

描述(申请人提供)：该计划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，来改进癌症患者的诊断和治疗。这项多学科计划强调利用系统的、高度平行的方法来描述人类癌症的分子特征，特别是使用DNA微阵列和组织微阵列来分析基因和蛋白质的表达模式。中心假设是，癌症之间或癌症与正常细胞之间的任何临床上重要的差异，都将伴随着相应的基因表达程序的差异。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，以及对细胞对癌症中重要的分子信号的反应的系统研究；(2)前列腺癌的研究，旨在了解先前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变化联系起来，并开发和评估新的预后标记；(3)对早期小型乳腺癌的全球基因表达和分子多样性进行研究，并对基于基因表达的预后标准在预测这些早期癌症的临床病程中的表现进行关键评估；以及(4)对软组织肉瘤的基因表达模式进行大规模系统研究，旨在开发用于诊断这些癌症的新的分子标志物和用于治疗这些癌症的新的分子靶点，并提高我们对作为癌症共同特征的间质增殖的认识。该方案得到一个支持、组织和监督项目的行政核心(核心C)和两个研究核心的支持--一个DNA微阵列信息学和生物统计学核心(核心A)，它将支持一个微阵列数据库，用于存档、分析和公开分发该项目的数据，并为数据分析提供专家咨询和支助；以及一个组织微阵列核心(核心B)，它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.