title: Genes associated with genotype-specific DNA methylation in squamous cell carcinoma as candidate drug targets.
abstract: BACKGROUND
  Aberrant DNA methylation is often associated with cancers. Thus, screening genes with cancer-associated aberrant DNA methylation is a useful method to identify candidate cancer-causing genes. Aberrant DNA methylation is also genotype dependent. Thus, the selection of genes with genotype-specific aberrant DNA methylation in cancers is potentially important for tailor-made medicine. The selected genes are important candidate drug targets.
  
  
  RESULTS
  The recently proposed principal component analysis based selection of genes with aberrant DNA methylation was applied to genotype and DNA methylation patterns in squamous cell carcinoma measured using single nucleotide polymorphism (SNP) arrays. SNPs that are frequently found in cancers are usually highly methylated, and the genes that were selected using this method were reported previously to be related to cancers. Thus, genes with genotype-specific DNA methylation patterns will be good therapeutic candidates. The tertiary structures of the proteins encoded by the selected genes were successfully inferred using two profile-based protein structure servers, FAMS and Phyre2. Candidate drugs for three of these proteins, tyrosine kinase receptor (ALK), EGLN3 protein, and NUAK family SNF1-like kinase 1 (NUAK1), were identified by ChooseLD.
  
  
  CONCLUSIONS
  We detected genes with genotype-specific DNA methylation in squamous cell carcinoma that are candidate drug targets. Using in silico drug discovery, we successfully identified several candidate drugs for the ALK, EGLN3 and NUAK1 genes that displayed genotype-specific DNA methylation.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Kinoshita
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Iwadate
authors.forename: Hideaki
authors.initials: H
authors.lastname: Umeyama
authors.forename: Y-h
authors.initials: YH
authors.lastname: Taguchi
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics*; D019295:Computational Biology; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D052138:Genes, Neoplasm / Q000235:genetics*; D005838:Genotype; D006801:Humans; D058990:Molecular Targeted Therapy; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide