The homeobox gene CDX2 in colorectal carcinoma: a genetic analysis

Accumulation of mutations in tumour suppressor genes and oncogenes has been proposed to underlie the initiation and progression of sporadic colorectal cancer (CRC). Evidence is accumulating to suggest that the caudal homeobox gene CDX2 is implicated in the pathogenesis of CRC. The CDX2 transcription factor is expressed in intestinal epithelium and is markedly down-regulate d in colon tumours. Furthermore, Cdx2 heterozygous null mice develop multip le intestinal tumours. In this present study, we have investigated CDX2 as a potential candidate gene for sporadic CRC by a thorough search of all exo ns and exon/intron boundaries for DNA polymorphisms and rare variants in a panel of CRC tumours. 6 polymorphisms were identified and the haplotypes de termined. In addition two rare variants were found, one of which was only i dentified in DNA from a CRC case. Loss of heterozygosity was observed in 3 out of 28 informative CRC cases. A possible association between particular haplotypes and tumour progression was also suggested by the data. In additi on a preliminary analysis of the relative expression of CDX2 alleles in tum our/normal tissue suggested some variation in the levels, however further a nalysis is required before any conclusions can be drawn. While CDX2 mutatio ns predisposing to sporadic CRC have not been identified, this study has es tablished that loss of CDX2 contributes towards the progression of some spo radic CRC tumours. (C) 2001 Cancer Research Campaign.