GSE117167
Tissue-specific transcriptomic and epigenomic profiles explain differential damage and repair of anti-cancer drug cisplatin induced DNA-adducts across mouse organs
Platinum-based drug cisplatin is a widely used first-line therapy for several cancers.  Cisplatin interacts with DNA mainly in the form of Pt-d(GpG) di-adduct, which stalls cell proliferation and activates DNA damage response pathway.  Cisplatin DNA-adducts are primarily repaired by nucleotide excision repair system.  Despite cisplatin shows a broad spectrum of anticancer activity, it has limitation of use due to acquired drug resistance and toxicity to nontargeted tissues.    By integrating genome-wide high-throughput “damage-seq”, “XR-seq”, mRNA-seq approaches along with epigenomic data we studied the mechanism of action of cisplatin across the mouse genome in kidney, liver, lung and spleen.    Genome-wide damage-seq data reveal that kidney is highest cisplatin-damage accumulation site, while spleen is lowest.  Excision repair on transcribed strand (TS) and non-transcribed strand (NTS) in active genes is in positive correlation with gene transcription, and regarding to nucleotide excision repair efficiency, there is no significant difference across organs.  Lastly, in response to cisplatin treatment ATM signaling is upregulated in kidney, liver and lung, while PKA signaling is downregulated across all organs.  The methodology and data we presented here include four different mouse organs and three “omics” data, it unbiasedly constitutes a foundation for understanding the mechanism of cellular respond to cisplatin and by means of improving chemotherapy while reducing side effect to normal tissues. Overall design: Damage-seq XR-seq and RNA-seq samples from 4 mouse organs after cispaltin injection in two replicates and RNA-seq from 4 organs in two replicates as control are collected. UPDATE: [Feb-14-2025] The annotation of Samples GSM3272787-GSM3272794 was corrected: All Samples originally labeled as 'control' were changed to 'cisplatin' and vice versa.