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NFIB is a driver of SCLC initiation, progression and metastasis in mouse and marks metastatic disease in patients

ABSTRACT: Small Cell Lung Cancer (SCLC) is the most aggressive type of lung cancer with early metastatic dissemination and invariable development of resistant disease for which no effective treatment is available to date. Mouse models of SCLC based on inactivation of Rb1 and Trp53 developed earlier showed frequent amplifications of two transcription factor genes: Nfib and Mycl. Overexpression of Nfib but not Mycl in SCLC mouse results in an enhanced and altered metastatic profile, and appears to be associated with genomic instability. NFIB promotes tumor heterogeneity with the concomitant expansive growth of poorly differentiated, highly proliferative, and invasive tumor cell populations. Consistent with the mouse data, NFIB expression in high-grade human neuroendocrine carcinomas correlates with advanced stage III/IV disease warranting its further assessment as a potentially valuable progression marker in a clinical setting.

ORGANISM(S): Mus musculus

PROVIDER: GSE82005 | GEO | 2016/07/29

SECONDARY ACCESSION(S): PRJNA323605

REPOSITORIES: GEO

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NFIB is a driver of SCLC initiation, progression and metastasis in mouse and marks metastatic disease in patients

Project description:Small Cell Lung Cancer (SCLC) is the most aggressive type of lung cancer with early metastatic dissemination and invariable development of resistant disease for which no effective treatment is available to date. Mouse models of SCLC based on inactivation of Rb1 and Trp53 developed earlier showed frequent amplifications of two transcription factor genes: Nfib and Mycl. Overexpression of Nfib but not Mycl in SCLC mouse results in an enhanced and altered metastatic profile, and appears to be associated with genomic instability. NFIB promotes tumor heterogeneity with the concomitant expansive growth of poorly differentiated, highly proliferative, and invasive tumor cell populations. Consistent with the mouse data, NFIB expression in high-grade human neuroendocrine carcinomas correlates with advanced stage III/IV disease warranting its further assessment as a potentially valuable progression marker in a clinical setting. Genomic DNA from mouse small cell lung tumor samples was analyzed by mate pair sequencing and low coverage sequencing. And RNA from Nfib overexpressing mouse small cell lung cancer cell lines was further analyzed for high quality RNA profiles using Illumina Hiseq2500. This series contains only RNA-seq data.

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