Ha Vu Tran1,2, Alexandra K Kiemer3, Volkhard Helms4. 1. Saarland University, Center for Bioinformatics, Saarbruecken, Germany. 2. Department of Computer Science, Faculty of Information Technology, Vietnam National University of Agriculture, Hanoi, Vietnam. 3. Saarland University, Department of Pharmacy, Pharmaceutical Biology, Saarbruecken, Germany. 4. Saarland University, Center for Bioinformatics, Saarbruecken, Germany volkhard.helms@bioinformatik.uni-saarland.de.
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. Copyright
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. Copyright
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