title: Integrated exon level expression analysis of driver genes explain their role in colorectal cancer.
abstract: Integrated analysis of genomic and transcriptomic level changes holds promise for a better understanding of colorectal cancer (CRC) biology. There is a pertinent need to explain the functional effect of genome level changes by integrating the information at the transcript level. Using high resolution cytogenetics array, we had earlier identified driver genes by 'Genomic Identification of Significant Targets In Cancer (GISTIC)' analysis of paired tumour-normal samples from colorectal cancer patients. In this study, we analyze these driver genes at three levels using exon array data--gene, exon and network. Gene level analysis revealed a small subset to experience differential expression. These results were reinforced by carrying out separate differential expression analyses (SAM and LIMMA). ATP8B1 was found to be the novel gene associated with CRC that shows changes at cytogenetic, gene and exon levels. Splice index of 29 exons corresponding to 13 genes was found to be significantly altered in tumour samples. Driver genes were used to construct regulatory networks for tumour and normal groups. There were rearrangements in transcription factor genes suggesting the presence of regulatory switching. The regulatory pattern of AHR gene was found to have the most significant alteration. Our results integrate data with focus on driver genes resulting in highly enriched novel molecules that need further studies to establish their role in CRC.
authors.affiliation: Medical Genomics, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
authors.forename: Mohammad Azhar
authors.initials: MA
authors.lastname: Aziz
authors.affiliation: Bioinformatics, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
authors.forename: Sathish
authors.initials: S
authors.lastname: Periyasamy
authors.affiliation: Surgery, National Guard Health Affairs, Riyadh, Saudi Arabia.
authors.forename: Zeyad
authors.initials: Z
authors.lastname: Al Yousef
authors.affiliation: Medical Genomics, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: AlAbdulkarim
authors.affiliation: Medical Genomics, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
authors.forename: Majed
authors.initials: M
authors.lastname: Al Otaibi
authors.affiliation: Medical Genomics, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
authors.forename: Abdulaziz
authors.initials: A
authors.lastname: Alfahed
authors.affiliation: Medical Genomics, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
authors.forename: Glowi
authors.initials: G
authors.lastname: Alasiri
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D017398:Alternative Splicing; D015415:Biomarkers / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D020732:Cytogenetic Analysis; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis
chemical_list: D015415:Biomarkers; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human