title: Identification of candidate driver genes in common focal chromosomal aberrations of microsatellite stable colorectal cancer.
abstract: Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Chromosomal instability (CIN) is a major driving force of microsatellite stable (MSS) sporadic CRC. CIN tumours are characterised by a large number of somatic chromosomal copy number aberrations (SCNA) that frequently affect oncogenes and tumour suppressor genes. The main aim of this work was to identify novel candidate CRC driver genes affected by recurrent and focal SCNA. High resolution genome-wide comparative genome hybridisation (CGH) arrays were used to compare tumour and normal DNA for 53 sporadic CRC cases. Context corrected common aberration (COCA) analysis and custom algorithms identified 64 deletions and 32 gains of focal minimal common regions (FMCR) at high frequency (>10%). Comparison of these FMCR with published genomic profiles from CRC revealed common overlap (42.2% of deletions and 34.4% of copy gains). Pathway analysis showed that apoptosis and p53 signalling pathways were commonly affected by deleted FMCR, and MAPK and potassium channel pathways by gains of FMCR. Candidate tumour suppressor genes in deleted FMCR included RASSF3, IFNAR1, IFNAR2 and NFKBIA and candidate oncogenes in gained FMCR included PRDM16, TNS1, RPA3 and KCNMA1. In conclusion, this study confirms some previously identified aberrations in MSS CRC and provides in silico evidence for some novel candidate driver genes.
authors.affiliation: Institute for Cancer Studies, Department of Oncology, Cancer Research UK/Yorkshire Cancer Research Sheffield Cancer Research Centre, University of Sheffield, Sheffield, United Kingdom.
authors.forename: George J
authors.initials: GJ
authors.lastname: Burghel
authors.affiliation: Institute for Cancer Studies, Department of Oncology, Cancer Research UK/Yorkshire Cancer Research Sheffield Cancer Research Centre, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Lin
authors.affiliation: Institute for Cancer Studies, Department of Oncology, Cancer Research UK/Yorkshire Cancer Research Sheffield Cancer Research Centre, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Whitehouse
authors.affiliation: Institute for Cancer Studies, Department of Oncology, Cancer Research UK/Yorkshire Cancer Research Sheffield Cancer Research Centre, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Brock
authors.affiliation: Academic Unit of Surgical Oncology, Department of Oncology, Cancer Research UK/Yorkshire Cancer Research Sheffield Cancer Research Centre, University of Sheffield, Sheffield, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Hammond
authors.affiliation: Department of Histopathology, Sheffield Teaching Hospitals Foundation Trust, Cancer Research UK/Yorkshire Cancer Research Sheffield Cancer Research Centre, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bury
authors.affiliation: Department of Infection and Immunity, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Stephenson
authors.affiliation: Institute for Cancer Studies, Department of Oncology, Cancer Research UK/Yorkshire Cancer Research Sheffield Cancer Research Centre, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Rina
authors.initials: R
authors.lastname: George
authors.affiliation: Institute for Cancer Studies, Department of Oncology, Cancer Research UK/Yorkshire Cancer Research Sheffield Cancer Research Centre, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Cox
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D052138:Genes, Neoplasm / Q000235:genetics*; D023281:Genomics; D006801:Humans; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D012008:Recurrence