title: Functionally-focused algorithmic analysis of high resolution microarray-CGH genomic landscapes demonstrates comparable genomic copy number aberrations in MSI and MSS sporadic colorectal cancer.
abstract: Array-based comparative genomic hybridization (aCGH) emerged as a powerful technology for studying copy number variations at higher resolution in many cancers including colorectal cancer. However, the lack of standardized systematic protocols including bioinformatic algorithms to obtain and analyze genomic data resulted in significant variation in the reported copy number aberration (CNA) data. Here, we present genomic aCGH data obtained using highly stringent and functionally relevant statistical algorithms from 116 well-defined microsatellites instable (MSI) and microsatellite stable (MSS) colorectal cancers. We utilized aCGH to characterize genomic CNAs in 116 well-defined sets of colorectal cancer (CRC) cases. We further applied the significance testing for aberrant copy number (STAC) and Genomic Identification of Significant Targets in Cancer (GISTIC) algorithms to identify functionally relevant (nonrandom) chromosomal aberrations in the analyzed colorectal cancer samples. Our results produced high resolution genomic landscapes of both, MSI and MSS sporadic CRC. We found that CNAs in MSI and MSS CRCs are heterogeneous in nature but may be divided into 3 distinct genomic patterns. Moreover, we show that although CNAs in MSI and MSS CRCs differ with respect to their size, number and chromosomal distribution, the functional copy number aberrations obtained from MSI and MSS CRCs were in fact comparable but not identical. These unifying CNAs were verified by MLPA tumor-loss gene panel, which spans 15 different chromosomal locations and contains 50 probes for at least 20 tumor suppressor genes. Consistently, deletion/amplification in these frequently cancer altered genes were identical in MSS and MSI CRCs. Our results suggest that MSI and MSS copy number aberrations driving CRC may be functionally comparable.
authors.affiliation: Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Kuwait University, Jabriya, Kuwait.|Research Division, Immunology Unit, Dasman Diabetes Institute (DDI), Dasman, Kuwait.
authors.forename: Hamad
authors.initials: H
authors.lastname: Ali
authors.affiliation: Research Division, Immunology Unit, Dasman Diabetes Institute (DDI), Dasman, Kuwait.|Department of Pharmacology & Toxicology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait.
authors.forename: Milad S
authors.initials: MS
authors.lastname: Bitar
authors.affiliation: Research Division, Immunology Unit, Dasman Diabetes Institute (DDI), Dasman, Kuwait.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Al Madhoun
authors.affiliation: Kuwait Medical Genetics Center, Kuwait City, Kuwait.
authors.forename: Makia
authors.initials: M
authors.lastname: Marafie
authors.affiliation: Molecular Pathology Unit, Department of Pathology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait.|Research Division, Genomics Unit, Dasman Diabetes Institute (DDI), Dasman, Kuwait.
authors.forename: Fahd
authors.initials: F
authors.lastname: Al-Mulla
mesh_terms: D000465:Algorithms; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D055028:Comparative Genomic Hybridization / Q000379:methods; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012007:Rectum / Q000473:pathology