Please use this identifier to cite or link to this item: doi:10.22028/D291-28049
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Title: Copy Number Alterations in Tumor Genomes Deleting Antineoplastic Drug Targets Partially Compensated by Complementary Amplifications
Author(s): Tran, Ha Vu
Kiemer, Alexandra
Helms, Volkhard
Language: English
Title: Cancer genomics & proteomics
Volume: 15
Issue: 5
Startpage: 365
Endpage: 378
Publisher/Platform: Inst.
Year of Publication: 2018
Publikation type: Journal Article
Abstract: BACKGROUND/AIM: Genomic DNA copy number alterations (CNAs) are frequent in tumors and have been catalogued by The Cancer Genome Atlas project. Emergence of chemoresistance frequently renders drug therapies ineffective. MATERIALS AND METHODS: We analyzed how CNAs recurrently found in the genomes of TCGA patients of thirty-one tumor types affect protein targets of antineoplastic (AN) agents. RESULTS: CNA deletions more frequently affected the targets of AN agents than CNA amplifications. Interestingly, in seven tumors we observed signs of compensatory CNAs. For example, in glioblastoma multiforme, two target genes (FLT1, FLT3) of the experimental drug sorafenib were recurrently deleted, whereas another target (KDR) of sorafenib was recurrently amplified. In renal clear cell carcinoma, the target FLT1 of pazopanib, sunitinib, sorafenib, and axitinib was recurrently deleted, whereas FLT4 bound by the same drugs, was recurrently amplified. CONCLUSION: Deletions of AN target proteins can be compensated by amplification of alternative targets.
DOI of the first publication: 10.21873/cgp.20095
Link to this record: hdl:20.500.11880/27483
ISSN: 1790-6245
Date of registration: 13-Jul-2019
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Pharmazie
Professorship: NT - Prof. Dr. Alexandra K. Kiemer
Collections:UniBib – Die Universitätsbibliographie

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