The homeobox gene CDX2 in colorectal carcinoma: a genetic analysis
File(s)
Author(s)
Type
Journal Article
Abstract
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-regulated in colon tumours. Furthermore, Cdx2 heterozygous null mice develop multiple intestinal tumours. In this present study, we have investigated CDX2 as a potential candidate gene for sporadic CRC by a thorough search of all exons and exon/intron boundaries for DNA polymorphisms and rare variants in a panel of CRC tumours. 6 polymorphisms were identified and the haplotypes determined. In addition two rare variants were found, one of which was only identified 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 addition a preliminary analysis of the relative expression of CDX2 alleles in tumour/normal tissue suggested some variation in the levels, however further analysis is required before any conclusions can be drawn. While CDX2 mutations predisposing to sporadic CRC have not been identified, this study has established that loss of CDX2 contributes towards the progression of some sporadic CRC tumours.
Date Issued
2001-01-16
Date Acceptance
2001-01-16
Citation
British Journal of Cancer, 2001, 84 (2), pp.218-225
ISSN
1532-1827
Publisher
Cancer Research UK
Start Page
218
End Page
225
Journal / Book Title
British Journal of Cancer
Volume
84
Issue
2
Copyright Statement
© 2001 Cancer Research Campaign
Subjects
Science & Technology
Life Sciences & Biomedicine
Oncology
ONCOLOGY
caudal related homeobox gene
CDX2
loss of heterozygosity
colorectal carcinoma
NONPOLYPOSIS COLON-CANCER
FAMILIAL ADENOMATOUS POLYPOSIS
INTESTINAL EPITHELIUM
TRANSCRIPTION FACTORS
INSULIN GENE
MUTANT MICE
EXPRESSION
MUTATIONS
HOMOLOG
PROTEIN
Adult
Aged
Aged, 80 and over
Alleles
Cohort Studies
Colorectal Neoplasms
DNA Mutational Analysis
DNA, Complementary
DNA, Neoplasm
Exons
Female
Gene Frequency
Haplotypes
Homeodomain Proteins
Humans
Introns
Loss of Heterozygosity
Male
Middle Aged
Mutation
Polymorphism, Genetic
Polymorphism, Single-Stranded Conformational
RNA Splicing
RNA, Neoplasm
Sequence Analysis, DNA
Trans-Activators
Oncology & Carcinogenesis
1112 Oncology And Carcinogenesis
Publication Status
Published