title: Novel genes associated with colorectal cancer are revealed by high resolution cytogenetic analysis in a patient specific manner.
abstract: Genomic abnormalities leading to colorectal cancer (CRC) include somatic events causing copy number aberrations (CNAs) as well as copy neutral manifestations such as loss of heterozygosity (LOH) and uniparental disomy (UPD). We studied the causal effect of these events by analyzing high resolution cytogenetic microarray data of 15 tumor-normal paired samples. We detected 144 genes affected by CNAs. A subset of 91 genes are known to be CRC related yet high GISTIC scores indicate 24 genes on chromosomes 7, 8, 18 and 20 to be strongly relevant. Combining GISTIC ranking with functional analyses and degree of loss/gain we identify three genes in regions of significant loss (ATP8B1, NARS, and ATP5A1) and eight in regions of gain (CTCFL, SPO11, ZNF217, PLEKHA8, HOXA3, GPNMB, IGF2BP3 and PCAT1) as novel in their association with CRC. Pathway and target prediction analysis of CNA affected genes and microRNAs, respectively indicates TGF-β signaling pathway to be involved in causing CRC. Finally, LOH and UPD collectively affected nine cancer related genes. Transcription factor binding sites on regions of >35% copy number loss/gain influenced 16 CRC genes. Our analysis shows patient specific CRC manifestations at the genomic level and that these different events affect individual CRC patients differently.
authors.affiliation: Bioinformatics, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
authors.forename: Hisham
authors.initials: H
authors.lastname: Eldai
authors.forename: Sathish
authors.initials: S
authors.lastname: Periyasamy
authors.forename: Saeed
authors.initials: S
authors.lastname: Al Qarni
authors.forename: Maha
authors.initials: M
authors.lastname: Al Rodayyan
authors.forename: Sabeena
authors.initials: S
authors.lastname: Muhammed Mustafa
authors.forename: Ahmad
authors.initials: A
authors.lastname: Deeb
authors.forename: Ebthehal
authors.initials: E
authors.lastname: Al Sheikh
authors.forename: Mohammed
authors.initials: M
authors.lastname: Afzal
authors.forename: Mohammed
authors.initials: M
authors.lastname: Afzal Khan
authors.forename: Mishal
authors.initials: M
authors.lastname: Johani
authors.forename: Zeyad
authors.initials: Z
authors.lastname: Yousef
authors.forename: Mohammad Azhar
authors.initials: MA
authors.lastname: Aziz
mesh_terms: D001665:Binding Sites; D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D020732:Cytogenetic Analysis; D056915:DNA Copy Number Variations; D005260:Female; D023281:Genomics / Q000379:methods*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D009857:Oncogenes; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism; D024182:Uniparental Disomy
chemical_list: D014157:Transcription Factors