ISSN:
1573-2568
Keywords:
DCC GENE
;
POLYMORPHISM
;
CODON 201
;
FLAT-TYPE COLORECTAL TUMOR
;
GENETIC MARKER
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Recent studies have identified the distinctexistence of flat-type colorectal tumors. The lowincidence of ras gene mutations in these tumors suggeststhat their genetic pathways of tumor progression may be different from those of the polypoid type.To elucidate further genetic alterations in flat-typecolorectal tumors, codon 201Arg/Glypolymorphism in the DCC (deleted in colorectalcarcinoma) gene was analyzed in normal tissue (normal colonicmucosa or peripheral lymphocytes) and in tumor tissuefrom 191 patients with colorectal tumors (36 patientswith flat-type colorectal tumors, 81 patients withpolypoid-type colorectal tumors, and 74 patients withadvanced carcinomas). For normal controls, 30 samplesobtained from patients who had neither colorectal tumors(confirmed by total colonoscopy) nor a family history of colorectal carcinoma were analyzed. DCC genecodon 201Arg/Gly polymorphism wasinvestigated by polymerase chain reaction-basedrestriction fragment length polymorphism analysis,fluorescence-based dideoxy sequencing, or both. For the flat type, thefrequency of codon 201Gly of the DCC gene was64% and 54% in the normal tissue of patients withadenoma with high-grade dysplasia and submucosalcarcinoma, respectively. It was 49%, 52%, and 49% in the normal tissueof patients with polypoid-type adenoma with high-gradedysplasia, submucosal carcinoma, and advanced carcinoma,respectively. In the normal tissue, codon 201Gly of the DCC gene was more frequentlyobserved in patients with flat-type adenoma withlow-grade dysplasia (67%) than in those withpolypoid-type adenoma with low-grade dysplasia (18%) orin normal controls (17%, P 〈 0.05, χ2test). Codon 201Arg/Gly polymorphism in tumortissues did not differ from that in the correspondingnormal tissues, except for 10 cases of carcinoma withloss of heterozygosity (LOH). In carcinomas with LOH, preferentialloss of the codon 201Arg allele was noted(9/10 cases). These results suggest that codon201Gly of the DCC gene is not only associatedwith flat-type colorectal tumors, but that it may serve as a usefulgenetic marker for identifying groups at higher risk forcolorectal cancer.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1018839907159
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