title: Copy number variants associated with 18p11.32, DCC and the promoter 1B region of APC in colorectal polyposis patients.
abstract: Familial Adenomatous Polyposis (FAP) is the second most common inherited predisposition to colorectal cancer (CRC) associated with the development of hundreds to thousands of adenomas in the colon and rectum. Mutations in APC are found in ~ 80% polyposis patients with FAP. In the remaining 20% no genetic diagnosis can be provided suggesting other genes or mechanisms that render APC inactive may be responsible. Copy number variants (CNVs) remain to be investigated in FAP and may account for disease in a proportion of polyposis patients. A cohort of 56 polyposis patients and 40 controls were screened for CNVs using the 2.7M microarray (Affymetrix) with data analysed using ChAS (Affymetrix). A total of 142 CNVs were identified unique to the polyposis cohort suggesting their involvement in CRC risk. We specifically identified CNVs in four unrelated polyposis patients among CRC susceptibility genes APC, DCC, MLH1 and CTNNB1 which are likely to have contributed to disease development in these patients. A recurrent deletion was observed at position 18p11.32 in 9% of the patients screened that was of particular interest. Further investigation is necessary to fully understand the role of these variants in CRC risk given the high prevalence among the patients screened.
authors.affiliation: Centre for Information-Based Medicine, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, 2305, Australia; School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, New South Wales, 2308, Australia.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Masson
authors.affiliation: Centre for Information-Based Medicine, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, 2305, Australia; School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, New South Wales, 2308, Australia.
authors.forename: Bente A
authors.initials: BA
authors.lastname: Talseth-Palmer
authors.affiliation: Centre for Information-Based Medicine, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, 2305, Australia; School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, New South Wales, 2308, Australia.
authors.forename: Tiffany-Jane
authors.initials: TJ
authors.lastname: Evans
authors.affiliation: Centre for Public Health, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, 2305, Australia; School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, New South Wales, 2308, Australia.
authors.forename: Patrick
authors.initials: P
authors.lastname: McElduff
authors.affiliation: Hunter Family Cancer Service, Hunter New England Area Health, Newcastle, New South Wales, 2305, Australia; University of NSW, St Vincent's Hospital Clinical School, Sydney, New South Wales, 2010, Australia; Hereditary Cancer Clinic, St Vincent's Hospital, The Kinghorn Cancer Centre, Sydney, New South Wales, 2010, Australia.
authors.forename: Allan D
authors.initials: AD
authors.lastname: Spigelman
authors.affiliation: CSIRO Food and Nutrition Flagship, North Ryde, New South Wales, 2113, Australia.
authors.forename: Garry N
authors.initials: GN
authors.lastname: Hannan
authors.affiliation: Centre for Information-Based Medicine, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, 2305, Australia; School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, New South Wales, 2308, Australia; Division of Molecular Medicine, Hunter Area Pathology Service, John Hunter Hospital, Newcastle, New South Wales, 2305, Australia.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
keywords: ALL, acute lymphoblastic leukaemia; BH, Bengamini and Hochberg; CHAS, Chromosome Analysis Suite; CN, copy number; CNV; CNV, copy number variation; COSMIC, Catalogue of Somatic Mutations in Cancer; CRC, colorectal cancer; Cancer; DGV, Database of genomic variants; DNA, deoxyribose nucleic acid; FAP, familial adenomatous polyposis; HMDD, human microRNA disease database; KEGG, Kyoto Encyclopaedia of Genes and Genomes; Kb, kilobase; LOH, loss of heterozygosity; MLPA, multiplex ligation-dependant probe amplification; MMR, mismatch repair; NTC, no template control; QC, quality control; RNA, ribose nucleic acid; SNP, single nucleotide polymorphism; TAM, Tool for the annotation of microRNAs; TCGA, The Cancer Genome Atlas; UCSC, University of California, Santa Cruz; diagnostic testing; lncRNA, link RNA; long non-coding RNAs; mapd, median absolute pairwise difference; miR, microRNA; ng, nanogram; polyposis