title: Impact of SNPs on CpG Islands in the MYC and HRAS oncogenes and in a wide variety of tumor suppressor genes: A multi-cancer approach.
abstract: Single nucleotide polymorphisms (SNPs) that occur within CpG Islands may lead to increased hypermethylation if a SNP allele has the potential to form a CpG dinucleotide, as well as potentially lead to hypomethylation if a SNP allele eliminates a CpG dinucleotide. We analyzed CpG-related SNP allele frequencies in whole genome sequences (WGS) across 5 TCGA cancer datasets, thereby exploiting a more recent appreciation for signaling pathway degeneracy in cancer. The cancer data sets were analyzed for SNPs in CpG islands associated with the oncogenes, HRAS and MYC, and in the CpG islands associated with the tumor suppressor genes, APC, DCC, and RB1. We determined that one SNP allele (rs3824120) in a CpG island associated with MYC which eliminated a CpG was more common in the cancer datasets than in the 100Genomes databases (p < 0.01). For HRAS, 2 SNP alleles (rs112690925, rs7939028) that created CpG's occurred significantly less frequently in the cancer data sets than in the general SNP databases (e.g., rs7939028, p < 0.0002, in comparison with AllSNPs(142)). Also, one SNP allele (rs4940177) that created a CpG in a CpG island associated with the DCC tumor suppressor gene, was more common in the cancer datasets (p < 0.0007). To understand a broader picture of the potential of SNP alleles to create CpG's in CpG islands of tumor suppressor genes, we developed a scripted algorithm to assess the SNP alleles associated with the CpG islands of 43 tumor suppressor genes. The following tumor suppressor genes have the possibility of significant, percent increases in their CpG counts, depending on which SNP allele(s) is present: VHL, BRCA1, BRCA2, CHEK2, PTEN and RB1.
authors.affiliation: a Department of Molecular Medicine , Morsani College of Medicine, University of South Florida , Tampa , FL , USA.
authors.forename: Mohammad D
authors.initials: MD
authors.lastname: Samy
authors.affiliation: a Department of Molecular Medicine , Morsani College of Medicine, University of South Florida , Tampa , FL , USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Yavorski
authors.affiliation: a Department of Molecular Medicine , Morsani College of Medicine, University of South Florida , Tampa , FL , USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Mauro
authors.affiliation: a Department of Molecular Medicine , Morsani College of Medicine, University of South Florida , Tampa , FL , USA.|b Immunology Program, Moffitt Cancer Center and Research Institute , Tampa , FL , USA.
authors.forename: George
authors.initials: G
authors.lastname: Blanck
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D000465:Algorithms; D000483:Alleles; D001483:Base Sequence; D019295:Computational Biology; D018899:CpG Islands; D000075389:DCC Receptor; D019175:DNA Methylation; D066264:Datasets as Topic; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D056286:Retinoblastoma Binding Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D000075389:DCC Receptor; C501909:DCC protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C000606393:RB1 protein, human; D011956:Receptors, Cell Surface; D056286:Retinoblastoma Binding Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: BLCA; CGHUB; COAD; CpG islands; DCC; ESCA; LUAD; MYC; SNPs; TCGA; algorithm; bioinformatics; cancer; methylation; oncogenes; tumor suppressor genes