Lung Adenocarcinoma Invasion Genomics

肺腺癌侵袭基因组学

基本信息

批准号：
8642149
负责人：
PIERRE P. MASSION
金额：
$ 54.97万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8642149
关键词：
Address Adenocarcinoma Animal Model Basement membrane Biological Biological Assay Biological Markers Biology Biopsy Specimen Blood Vessels Cell Mobility Cell-Cell Adhesion Cells Chromosomes Clinical Clinical Management Coculture Techniques Complex DNA DNA Microarray Chip DNA copy number Data Data Analyses Data Set Diagnosis Diagnostic Diagnostic Neoplasm Staging Disease Early treatment Epidemiology Epidermal Growth Factor Receptor Excision Extravasation Fine needle aspiration biopsy Fluorescent in Situ Hybridization Gene Amplification Gene Expression Gene Expression Alteration Gene Expression Profiling Gene Targeting Genes Genetic Transcription Genomics Goals Heterogeneity Histologic Indolent Lung Lung Adenocarcinoma Lung Neoplasms Malignant Neoplasms Malignant neoplasm of lung Measurement Measures Mediating Messenger RNA Molecular Mutation Needle biopsy procedure Neoplasm Metastasis Nodule Outcome Patients Phase Phenotype Process Property RNA RNA Interference Research Resected Risk Role Solid Somatic Mutation Specimen Staging Stromal Cells System Testing The Cancer Genome Atlas Therapeutic Tissue Microarray Tissues Tumor stage Validation advanced disease angiogenesis cell motility clinically relevant cohort exome sequencing experience improved innovation multidisciplinary neoplastic cell novel prospective public health relevance repository research clinical testing tumor tumor progression

项目摘要

DESCRIPTION (provided by applicant): Our project focuses on characterizing the molecular mechanisms important for the acquisition of invasion in lung adenocarcinoma. Our research has focused on characterizing the molecular mechanisms important for invasion, the initial step of metastasis. Studies from our group and others indicate that clinical outcomes for patients with early stage lung adenocarcinoma are influenced by histological invasiveness. Deciphering the molecular processes underlying the acquisition of invasiveness promises to have increasing importance as we see a shift in the epidemiology of lung cancer towards early, and in some cases, not yet invasive disease. An improved understanding of the biological properties of these tumors will enhance the clinical management of early stage lung cancer, including directing the extent of resection for small lung adenocarcinoma tumors. Our dataset is enriched for early stage non-invasive adenocarcinoma (AIS, formerly called BAC) tumors that are not well represented in genomics repositories such as The Cancer Genome Atlas (TCGA). Our preliminary gene expression profiling results from tumor cells suggest that focal chromosomal copy number increase is important in mediating the acquisition of invasion in lung adenocarcinoma. This innovative discovery is the focus of this multidisciplinary, multi-institutional project to expand our genomics examination of focal somatic copy number alterations, examine the role of stromal influences on invasion, investigate the diagnostic and therapeutic implications of gene amplification, and to understand the mechanisms that repress invasion in AIS and promote invasion in adenocarcinoma. Using well characterized cohorts of lung adenocarcinoma specimens, we will use RNA and DNA microarrays, whole exome sequencing, and fluorescent in situ hybridization to test the hypothesis that genomic loci with integrated alterations of copy number and mRNA levels are important for the acquisition of invasion and metastasis capacity in lung adenocarcinoma. Upon validation in resected specimens, these loci will be brought forth for prospective clinical testing in resected tumor specimens and in fine needle aspirates acquired from early stage lung adenocarcinoma tumors. Our long term goal is to develop biomarkers that will stratify risk before or after resection of tumors that are homogenous radiographically or histologically, respectively.

描述（由申请人提供）：我们的项目着重于表征对肺腺癌侵袭至关重要的分子机制。我们的研究重点是表征对侵袭至关重要的分子机制，这是转移的第一步。我们小组和其他人的研究表明，早期肺腺癌患者的临床结局受组织学侵入性的影响。消除侵入性的基本过程破译的分子过程有望提高重要性，因为我们看到肺癌的流行病学转变向早期，在某些情况下却没有侵入性疾病。对这些肿瘤的生物学特性的提高了解将增强早期肺癌的临床管理，包括指导小肺腺癌肿瘤的切除程度。我们的数据集富含早期的非侵入性腺癌（AIS，以前称为BAC）肿瘤，这些肿瘤在基因组学存储库中并未很好地表示，例如癌症基因组图集（TCGA）。我们的初步基因表达分析是由肿瘤细胞引起的，表明局灶性染色体拷贝数的增加对于介导肺腺癌中侵袭的获取很重要。这一创新的发现是这个多学科的多机构项目的重点，旨在扩大我们对局灶性体细胞拷贝数变化的基因组学检查，检查基质影响对入侵的作用，研究基因扩增的诊断和治疗性含义，并了解在AIS中抑制Isis Ins Intesion Inscasion Invasion Invasion Incasion inenecarcarcarlicoma的机制。使用良好的肺腺癌标本的同类群体，我们将使用RNA和DNA微阵列，整个外显子组测序以及荧光原位杂交来测试假说，即具有拷贝数和mRNA综合变化的基因组基因概念对入侵和MERNA水平的综合变化对于获得lung adeneNopary in lung adeneCarcarso composition coppy和mRNA水平很重要。在切除的样品中进行验证后，这些基因座将在切除的肿瘤标本中进行前瞻性临床测试，以及从早期肺腺癌肿瘤中获得的细针抽吸物中的吸入。我们的长期目标是开发生物标志物，该生物标志物将分别在同学或组织学上分别切除肿瘤之前或之后分层风险。