DOI: 10.1101/517169Jan 10, 2019Paper

A novel role for the tumor suppressor gene ITF2 in lung tumorigenesis and chemotherapy response

BioRxiv : the Preprint Server for Biology
Olga PerniaInmaculada Ibanez de Caceres

Abstract

Despite often leading to platinum resistance, platinum-based chemotherapy continues to be the standard treatment for many epithelial tumors. In this study we analyze the cytogenetic alterations that arise after cisplatin treatment providing novel insights into the molecular biology and the cellular mechanisms involved in the acquired resistance in these tumor types. Methods: In this study, we used 1 million array-CGH and qRT-PCR methodologies to identify and validate cytogenetic alterations that arise after cisplatin treatment in four lung and ovarian paired cisplatin-sensitive/resistant cell lines. We used whole transcriptome sequencing (RNA-seq), functional transfection assays and gene-pathway activity analysis in our experimental cellular models and in fresh frozen primary NSCLC tumors to identify genes with a potential role in the development of this malignancy. Results were further explored in 55 lung and ovarian primary tumors and control samples and in two extensive in silico databases (TCGA and KMplotter) with 1,926 NSCLC and 1,425 additional epithelial tumors. Results: Long-term cell exposure to platinum induces the frequent deletion of ITF2 gene. Restoration of ITF2 expression re-sensitizes tumor cells to platinum and...Continue Reading

Related Concepts

Malignant Neoplasms
Non-Small Cell Lung Carcinoma
Cisplatin
Down-Regulation
Gene Deletion
Genes
Lung
Ovarian Carcinoma
Tumor Suppressor Genes
Cell Line, Tumor

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