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Identification of c...
Identification of candidate SNPs for drug induced toxicity from differentially expressed genes in associated tissues
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- Hasmats, Johanna (författare)
- KTH,Genteknologi,Science for Life Laboratory, SciLifeLab,Royal Institute Technology, Sweden
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- Kupershmidt, Ilya (författare)
- KTH,Genteknologi,Science for Life Laboratory, SciLifeLab,NextBio, CA 95050 USA Royal Institute Technology, Sweden
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- Rodriguez-Antona, Cristina (författare)
- Spanish National Cancer Centre CNIO, Spain
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- Jane Su, Qiaojuan (författare)
- NextBio, CA 95050 USA
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- Suleman Khan, Muhammad (författare)
- Linköpings universitet,Avdelningen för läkemedelsforskning,Hälsouniversitetet
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- Jara, Carlos (författare)
- Fdn Hospital Alcorcon FHA, Spain
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- Mielgo, Xabier (författare)
- Fdn Hospital Alcorcon FHA, Spain
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- Lundeberg, Joakim (författare)
- KTH,Genteknologi,Science for Life Laboratory, SciLifeLab,Royal Institute Technology, Sweden
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- Green, Henrik (författare)
- KTH,Linköpings universitet,Klinisk farmakologi,Hälsouniversitetet,Genteknologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- Elsevier, 2012
- 2012
- Engelska.
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Ingår i: Gene. - : Elsevier. - 0378-1119 .- 1879-0038. ; 506:1, s. 62-68
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- The growing collection of publicly available high-throughput data provides an invaluable resource for generating preliminary in silico data in support of novel hypotheses. In this study we used a cross-dataset meta-analysis strategy to identify novel candidate genes and genetic variations relevant to paclitaxel/carboplatin-induced myelosuppression and neuropathy. We identified genes affected by drug exposure and present in tissues associated with toxicity. From ten top-ranked genes 42 non-synonymous single nucleotide polymorphisms (SNPs) were identified in silico and genotyped in 94 cancer patients treated with carboplatin/paclitaxel. We observed variations in 11 SNPs, of which seven were present in a sufficient frequency for statistical evaluation. Of these seven SNPs. three were present in ABCA1 and ATM, and showed significant or borderline significant association with either myelosuppression or neuropathy. The strikingly high number of associations between genotype and clinically observed toxicity provides support for our data-driven computations strategy to identify biomarkers for drug toxicity.
Ämnesord
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
Nyckelord
- Paclitaxel
- Carboplatin
- Single nucleotide polymorphism
- Toxicity
- Gene expression microarrays
- Meta-analysis
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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