title: A genome-wide study of cytogenetic changes in colorectal cancer using SNP microarrays: opportunities for future personalized treatment.
abstract: In colorectal cancer (CRC), chromosomal instability (CIN) is typically studied using comparative-genomic hybridization (CGH) arrays. We studied paired (tumor and surrounding healthy) fresh frozen tissue from 86 CRC patients using Illumina's Infinium-based SNP array. This method allowed us to study CIN in CRC, with simultaneous analysis of copy number (CN) and B-allele frequency (BAF)--a representation of allelic composition. These data helped us to detect mono-allelic and bi-allelic amplifications/deletion, copy neutral loss of heterozygosity, and levels of mosaicism for mixed cell populations, some of which can not be assessed with other methods that do not measure BAF. We identified associations between CN abnormalities and different CRC phenotypes (histological diagnosis, location, tumor grade, stage, MSI and presence of lymph node metastasis). We showed commonalities between regions of CN change observed in CRC and the regions reported in previous studies of other solid cancers (e.g. amplifications of 20q, 13q, 8q, 5p and deletions of 18q, 17p and 8p). From Therapeutic Target Database, we identified relevant drugs, targeted to the genes located in these regions with CN changes, approved or in trials for other cancers and common diseases. These drugs may be considered for future therapeutic trials in CRC, based on personalized cytogenetic diagnosis. We also found many regions, harboring genes, which are not currently targeted by any relevant drugs that may be considered for future drug discovery studies. Our study shows the application of high density SNP arrays for cytogenetic study in CRC and its potential utility for personalized treatment.
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Farzana
authors.initials: F
authors.lastname: Jasmine
authors.forename: Ronald
authors.initials: R
authors.lastname: Rahaman
authors.forename: Charlotte
authors.initials: C
authors.lastname: Dodsworth
authors.forename: Shantanu
authors.initials: S
authors.lastname: Roy
authors.forename: Rupash
authors.initials: R
authors.lastname: Paul
authors.forename: Maruf
authors.initials: M
authors.lastname: Raza
authors.forename: Rachelle
authors.initials: R
authors.lastname: Paul-Brutus
authors.forename: Mohammed
authors.initials: M
authors.lastname: Kamal
authors.forename: Habibul
authors.initials: H
authors.lastname: Ahsan
authors.forename: Muhammad G
authors.initials: MG
authors.lastname: Kibriya
mesh_terms: D000483:Alleles; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000628:therapy; D030541:Databases, Genetic; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009030:Mosaicism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D057285:Precision Medicine