Identification of evolutionarily conserved DNA damage response genes that alter sensitivity to cisplatin

• DOI: 10.18632/oncotarget.13353
• Publication Date: 2016-11-15T21:57:42Z
• Authors: Anna V. Gaponova; Alexander Y. Deneka; Tim N. Beck; Hanqing Liu; Gregory Andrianov; Anna S. Nikonova; Emmanuelle Nicolas; Margret B. Einarson; Erica A. Golemis; Ilya G. Serebriiskii
• Keywords: 0303 health sciences; DNA Repair; Gene Expression Profiling; Resistance; Blotting, Western; Fluorescent Antibody Technique; High-Throughput Nucleotide Sequencing; Antineoplastic Agents; 612; DNA damage response; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Drug Resistance, Neoplasm; Cell Line, Tumor; Platinating agents; Animals; Cluster Analysis; Humans; Cisplatin; Head and neck cancer; Transcriptome; Research Paper; DNA Damage

// Anna V. Gaponova 1, 2 , Alexander Y. Deneka Tim N. Beck 3 Hanqing Liu 4 Gregory Andrianov S. Nikonova 1 Emmanuelle Nicolas Margret B. Einarson Erica A. Golemis Ilya G. Serebriiskii Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA Department of Biochemistry and Biotechnology, Kazan Federal University, 420008, Russian Federation & Biology, Program in Cell Biology Genetics, Drexel University College Medicine, 19129, Pharmaceutics, Jiangsu School Pharmacy, Jingkou District Zhenjiang, 212013, China Correspondence to: Serebriiskii, email: [e-mail] Golemis, [e-mail] Keywords: platinating agents, resistance, DNA damage response, head neck cancer Received: September 08, 2016 Accepted: October 27, Published: November 15, ABSTRACT Ovarian, neck, other cancers are commonly treated with cisplatin damaging cytotoxic agents. Altered response (DDR) contributes to resistance these tumors chemotherapies, some targeted therapies, radiation. DDR involves multiple protein complexes signaling pathways, which evolutionarily ancient involve orthologs conserved from yeast humans. To identify new regulators cisplatin-resistance human tumors, we integrated high throughput curated datasets describing genes that regulate sensitivity and/or ionizing Next, clustered highly validated based on chemogenomic profiling, then mapped expanded genomic networks for metazoans, including This approach identified an enriched candidate set involved the regulation radiation Direct functional assessment selected using RNA interference confirmed their activity influencing degree γH2AX focus formation ATR phosphorylation, ovarian cell lines, suggesting impaired as driving mechanism. work enlarges may contribute chemotherapy provides a contextual resource interpreting next generation sequencing (NGS) profiling tumors.