Since allelic loss of genes involved in the development of colorectal cancer could serve as prognostic markers, we examined the correlation between loss of markers linked to the hMSH2/hMSH6 (2p21-16.3), hMLH1 (3p21.3), APC (5q21-22), p53 (17p13.1) and DCC (18q21.3) loci and survival in a series of 64 consecutively collected colorectal cancers.
It was subsequently shown that somatic mutations of these genes (APC, mismatch repair genes, TP53, KRAS, and DCC) also occur in sporadic colorectal cancer.
Whether or not the deleted in colorectal cancer (DCC) gene is implicated in metastases or in predicting prognosis in patients with colorectal cancer has not previously been substantiated.
These data suggest that the carcinogenetic pathways of protruding and superficial depressed colorectal cancers are different, and that alterations of tumor suppressor gene(s) located on 18q21 other than Smad2, Smad4 and DCC might be associated with most superficial depressed colorectal cancers.
Alterations of DCC gene were analyzed in stage-matched two panels of 30 RER+ and 30 RER- colorectal cancers using semiquantitative reverse transcription-PCR and PCR-LOH analyses.
Allelic imbalance and microsatellite instability of the DCC gene in colorectal cancer in patients under the age of 35 using fluorescent DNA technology.
Protein expression of the putative tumour-suppressor gene DCC on chromosome 18q was evaluated in a panel of 16 matched colorectal cancer and normal colonic tissue samples together with DCC mRNA expression and allelic deletions (loss of heterozygosity, LOH).
Allelic loss of a portion of chromosome 18q and lack of expression of deleted in colorectal cancer (DCC) protein has been reported as an adverse prognostic indicator for stage II (i.e., Dukes' B2) colorectal cancer.
These results suggest that codon 201Gly of the DCC gene is not only associated with flat-type colorectal tumors, but that it may serve as a useful genetic marker for identifying groups at higher risk for colorectal cancer.
DCC was initially identified and cloned during a search for the target gene located in a region of 18q that demonstrated loss of heterozygosity (LOH) in 70 to 80% of colorectal cancers.
These findings indicate that the loss of one chromosome 18 is an important mechanism producing allelic deletion of the DCC gene in colorectal carcinomas.
Although little is known of the specific mechanisms that account for the loss of its expression in most cancers, the recent studies demonstrating an association between loss of DCC expression in colorectal cancers and poor prognosis imply that DCC inactivation may have very significant effects on the cancer cell phenotype.
Twenty-five of 84 tumors had homozygous deletions at 18q21.1, a site that excludes DCC (a candidate suppressor gene for colorectal cancer) and includes DPC4, a gene similar in sequence to a Drosophila melanogaster gene (Mad) implicated in a transforming growth factor-beta (TGF-beta)-like signaling pathway.
Inactivation of the "deleted in colon cancer" (DCC) gene on chromosome 18 is known to be associated with the tumorigenesis and metastasis of colorectal cancer.
The current study indicated that detection of allelic loss of DCC and absence of Ki-ras codon 12 mutations are associated with the metastatic potential of colorectal carcinoma in the liver.
The data recorded in our series differ from other authors' data in three respects: a high incidence of pseudodiploid chromosome number, rearrangements of chromosome 19 and 15, and involvement of DCC gene in the development of gastric cancer, as well as in colorectal cancer as previously reported.
The clinical application of molecular genetics (i.e., RFLP analysis of chromosome 17p, 18q, and 22q and RT-PCR analysis of DCC expression into messenger RNA) can be used to determine the metastatic potential of colorectal carcinomas.
Thirty-one human bladder transitional cell carcinomas (TCCs) were examined for allelic loss at five chromosome 18q loci, including the DCC gene (deleted in colorectal carcinoma) and at chromosome 11p15 in a restriction fragment length polymorphism analysis.
In order to examine whether the deletion of the putative cell adhesion molecule DCC is related to the level of GJIC, which might, in turn, be important in human colorectal cancers, we compared levels of expression of the DCC gene with the GJIC capacity of a panel of human colorectal adenocarcinoma cell lines isolated from different stages of tumor progression.
In addition, all 4 specimens of colorectal cancer with liver metastasis showed the decreased expression level of DCC mRNA, suggesting that functional loss of DCC in cancerous tissues may play an important role in metastatic events.