The ��methylation status�� data column in Table 1 reflects these 2 situations (e.g., Hypo/New ceritinib novartis for a single gene, in a particular tissue). Analysis of sequenced AP-PCR products. The sequences were subjected to BLAT database searches of the mouse genome (UCSC Genome Browser, July 2007 mouse assembly (http://genome.ucsc.edu/cgi-bin/hgBlat?command=start&org=mouse) in order to ascertain in which regions of the genome the unique PB-induced precancerous and tumor RAMs occurred. The BLAT program aligns a nucleotide or amino acid sequence to an index of an entire animal genome. For DNA sequence queries, BLAT can detect sequence alignments of 95% or greater similarity of regions with lengths of 25 or more base pairs.
Additional information about the genomic region/gene is listed, including, but not limited to: gene information, sequence conservation between species, GC percentage, and the location of single nucleotide polymorphisms and repeat elements. The unique RAMs were classified according to a scheme that indicates where, in relation to a gene (e.g., within an intron, within an exon, upstream of the transcriptional start site), they are located. RAMs were also categorized by chromosomal location and gene function. Gene Ontology information for Supplemental Figure S5 was obtained from http://www.geneontology.org/. The functions of the genes identified using BLAT searches were investigated via Pathway Studio 5.0 (Ariadne Genomics, Rockville, MD). In this fashion, connections between each individual gene and other genes, cellular processes, or disease states were elucidated.
For a subset of the genes, examples of these analyses are located in Supplemental Figures S6-S9. In addition, common targets and common regulators of genes identified from unique RAMs in both the precancerous and tumor tissue were discerned. Pathway Studio 5.0 was also utilized to uncover documented links between unique precancerous and tumor RAMs and cancer-related processes, including angiogenesis, apoptosis, epithelial-mesenchymal cell transition (EMT), migration/invasion/metastasis and growth and survival. Comparison of Genes/Genomic Regions Identified from Unique PB-Induced RAMs that Formed in both CAR WT (Precancerous Liver and/or Liver Tumor) to Genes/Genomic Regions Identified from Unique PB-induced RAMs in Liver Tumor�CSusceptible B6C3F1 Mice (2 and/or 4 Weeks) We previously identified 170 total unique RAMs in livers of tumor-susceptible B6C3F1 mice treated with 0.
05% (wt/wt) PB for 2 or 4 weeks, as compared with the resistant C57BL/6 stock (Bachman et al., 2006b), and PCR products representing 90 of these 170 (53%) RAMs were cloned and subjected to BLAT searches that resulted in 51 annotated genes (Phillips and Goodman, 2008). Unique B6C3F1 RAMs at 2 and 4 weeks, which corresponded to identical Batimastat genes and uncharacterized regions (i.e.