2 research outputs found
Identification of Candidate Driver Genes in Common Focal Chromosomal Aberrations of Microsatellite Stable Colorectal Cancer
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 gene