Gene expression differences between the microsatellite instability (MIN) and chromosomal instability (CIN) phenotypes in colorectal cancer revealed by high-density cDNA array hybridization.
Two distinct pathways of tumorigenesis exist in sporadic colorectal cancer. The microsatellite instability pathway (MIN), which is characterized by widespread microsatellite instability due to aberrant mismatch repair machinery, accounts for 15% of all sporadic colorectal cancers. The chromosomal instability (CIN) phenotype, which accounts for 85% of sporadic colorectal cancers, is characterized by gross chromosomal lesions but the underlying mechanism remains unclear. We have addressed differences in gene expression between the MIN and CIN colorectal cancer phenotypes in vitro by the use of high density cDNA filters to compare gene expression patterns between MIN and CIN colorectal cancer cell-lines yielding a panel of 73 consistently differentially expressed genes. Nine of these genes were subjected to confirmatory analysis by independent methods, of which six were confirmed as being differentially expressed; PLK, RanBP2 and CCNA2 were overexpressed in CIN lines while BTF3, H2AZ and PTPD1 were overexpressed in MIN lines. These six genes are involved in diverse processes, such as maintenance of chromatin architecture, DNA-damage checkpoint and cell cycle regulation, which may contribute to the CIN and MIN phenotypes.
Dunican
Donncha S
DS
Department of Biochemistry, Royal College of Surgeons in Ireland, 123 St Stephens' Green, Dublin 2, Ireland.
McWilliam
Peter
P
Tighe
Orna
O
Parle-McDermott
Anne
A
Croke
David T
DT
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D002843:Chromatin / Q000378:metabolism / Q000648:ultrastructure; D019457:Chromosome Breakage / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004249:DNA Damage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018895:Microsatellite Repeats; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D014407:Tumor Cells, Cultured / Q000378:metabolism
D002843:Chromatin; D009363:Neoplasm Proteins