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Identification and characterization of driver gene(s) in recurrent lung cancer am

复发性肺癌驱动基因的鉴定和表征

基本信息

批准号：
8301736
负责人：
David Mu
金额：
$ 26.54万
依托单位：
EASTERN VIRGINIA MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-08 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8301736
关键词：
14q13 Address Area Biological Assay Candidate Disease Gene Clinical Collaborations DNA copy number Data Data Set Diagnosis Diagnostic Epithelial Cells Evaluation Future Gene Expression Genes Genome Genomics Gleevec Goals Growth In Vitro KRAS2 gene Laboratories Libraries Lung Malignant Neoplasms Malignant neoplasm of lung Methods Molecular Oligonucleotides Oncogenes RNA Interference RNA library Recurrence Representational Oligonucleotide Microarray Analysis Research Research Personnel Research Proposals Resolution Roche brand of trastuzumab Sampling Squamous cell carcinoma Technology Tumorigenicity Work base cancer cell design follow-up gain of function gene function genome-wide in vivo insight loss of function lung carcinogenesis new therapeutic target novel overexpression prognostic success therapeutic target tool transcription factor

项目摘要

DESCRIPTION (provided by applicant): We have completed analysis of over 250 lung cancer samples by a high- resolution genome profiling method developed here at Cold Spring Harbor Laboratory (CSHL). We found twelve major recurrent amplicons, most of which contain known driver genes such as MYC or KRAS2, and three others that do not, including the second most frequent amplicon which is located at 14q13. Our first specific aim is to perform comprehensive functional evaluation of all three candidate driver genes within this frequently amplified region at 14q13. This comprehensive functional evaluation will utilize both gain-of-function transformation assays and loss-of-function assays using new RNA interference technology, developed here at CSHL, that silences gene expression in vitro and in vivo. We have preliminary data that indicates that all three genes, each encoding a different transcription factors, synergistically promote the proliferation of lung epithelial cells. In addition to functional analysis, we have formed collaborations to address the potential diagnostic and prognostic significance of 14q13 amplification. The other two novel frequent amplicons contain several candidate genes. To address the difficulty inherent in functional analysis of amplicons containing many overexpressed genes, our second specific aim is to develop new barcoded RNA library interference technology, which enables functional analysis of many genes in parallel, into a robust tool for functional analysis of amplicons with large numbers of candidate driver genes. Our results will produce new insights into the molecular basis of lung carcinogenesis and should identify key therapeutic targets and new strategies for diagnostics for this highly lethal cancer. The first goal of this study focuses on the discovery and functional characterization of novel causal genes of one of the most deadly forms of lung cancer. The second goal is to create a gene function-based tool to enable researchers to rapidly identify the causal gene within a recurrent amplified genomic region that contains too many genes to be studied by a gene-by-gene approach. Forward research progress of this research proposal is expected to positively impact the diagnosis and treatment of lung cancer in the future. The first goal of this study focuses on the discovery and functional characterization of novel causal genes of one of the most deadly forms of cancers ¿ lung cancer. The second goal is to create a gene function-based tool to enable researchers to rapidly identify the causal gene within a recurrent amplified genomic region that contains too many genes to be studied by a gene-by-gene approach. Forward research progress of this research proposal is expected to positively impact the diagnosis and treatment of lung cancer in the future.