title: Screening for common copy-number variants in cancer genes.
abstract: For most cases of colorectal cancer that arise without a family history of the disease, it is proposed that an appreciable heritable component of predisposition is the result of contributions from many loci. Although progress has been made in identifying single nucleotide variants associated with colorectal cancer risk, the involvement of low-penetrance copy number variants is relatively unexplored. We have used multiplex amplifiable probe hybridization (MAPH) in a fourfold multiplex (QuadMAPH), positioned at an average resolution of one probe per 2 kb, to screen a total of 1.56 Mb of genomic DNA for copy number variants around the genes APC, AXIN1, BRCA1, BRCA2, CTNNB1, HRAS, MLH1, MSH2, and TP53. Two deletion events were detected, one upstream of MLH1 in a control individual and the other in APC in a colorectal cancer patient, but these do not seem to correspond to copy number polymorphisms with measurably high population frequencies. In summary, by means of our QuadMAPH assay, copy number measurement data were of sufficient resolution and accuracy to detect any copy number variants with high probability. However, this study has demonstrated a very low incidence of deletion and duplication variants within intronic and flanking regions of these nine genes, in both control individuals and colorectal cancer patients.
authors.affiliation: Institute of Genetics, School of Biology, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
authors.forename: Jess
authors.initials: J
authors.lastname: Tyson
authors.forename: Tamsin M O
authors.initials: TM
authors.lastname: Majerus
authors.forename: Susan
authors.initials: S
authors.lastname: Walker
authors.forename: John A L
authors.initials: JA
authors.lastname: Armour
mesh_terms: D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3; D015179:Colorectal Neoplasms / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D017353:Gene Deletion; D018628:Gene Dosage; D052138:Genes, Neoplasm; D014644:Genetic Variation; D006801:Humans; D007438:Introns; D008957:Models, Genetic; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D012306:Risk
chemical_list: D004247:DNA