These results suggest that the DCC gene is included in the allelic deletion on chromosome 18q, and that the progression of colorectal carcinoma from early stage to advanced stage accompanies the inactivation of the DCC gene through LOH and other mechanisms.
This hypothesis was based on the frequent involvement of the DCC gene in colorectal carcinoma and on the previously reported linkage between HNPCC and the Kidd blood group locus (JK) also on 18q.
While the DCC gene was expressed in most normal tissues, including colonic mucosa, its expression was greatly reduced or absent in most colorectal carcinomas tested.
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.
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.
These results suggest that concordant p53 and DCC alterations and inactivation of several other tumor-suppressor genes, especially those on chromosomes 13q and 14q, play important roles in the acquisition of metastatic potential of colorectal carcinoma.
Loss of heterozygosity detected in formalin-fixed, paraffin-embedded tissue of colorectal carcinoma using a microsatellite located within the deleted in colorectal carcinoma gene.
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.
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.
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.
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.
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.
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.
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 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.
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).