The mutation and deletion of APC, MCC genes in human esophageal cancer were analyzed by PCR amplification and direct sequencing assay. In PCR amplification analysis, one of 10 cases of esophageal ...cancer was found to have APC gene deletion in exon 11; one of 10 cases of EC was found to have MCC gene deletion in exon 12; one case of EC was found to have MCC gene deletion in exon 12. One of adjacent non-tumor tissue was also found to have deletion at exon 12 of MCC. In PCR direct sequencing analysis, two of 10 cases of EC were found to contain APC gene mutation in exon 11, two of 7 cases of EC were found to contain MCC genes mutation in exon 12. The results confirmed that mutation of APC and MCC genes exists in human esophageal cancer. It gives new clues to the understanding of carcinogenesis of human esophageal cancer. The mechanism of mutation or deletion of APC and MCC genes in EC needs further study.
The mutation and deletion of the multiple tumor suppressor genes, including p53, Rb, APC and MCC in the same tissue of humanesophageal cancer (EC) and adjacent non-tumor were analysed by PCR ...amplification and direct sequencing. In 10 cases of EC 6 were found mutations of p53 gene, 5 were found abnormality of Rb gene, 3 were found mutation of APC gene, 3 were found mutation of MCC gene, 8 were found atleration abnormality of tumor suppressor genes Rb, p53, APC and MCC, 6 were found two or more abnormality of the tumor suppressor genes. The results indicated that the alterations in multiple of tumor suppressor genes were related to carcinogenesis of human esophageal cancer.
Both deleted in colorectal carcinoma (DCC) and mutated in colorectal carcinomas (MCC) genes are newly found tumour suppresser genes in colorectal carcinomas. In this study mutations of DCC gene and ...loss of heterozygosity (LOH) of MCC gene were detected with Southern blot and PCR methods respectively. The study consisted of 30 cases of colorectal adenoma (10 with mild, 10 with moderate and 10 with severe dysplasia) and 33 cases of colorectal carcinomas (13 highly, 10 moderately and 10 poorly differentiated, meanwhile 9 in Dukes A, 10 in B and 14 in C stage). Their paired normal colorectal mucosa served as control. The results were as follows: mutation of DCC was not found in any specimen with normal mucosa or with adenoma of mild and moderate dysplaaia, while it was found in one if those with severe dysplasia. Mutation of DCC was, however, found in 7 of the 33 specimens with carcinoma and there was a correlation between the positive rate and the differentiation or staging of the carcinoma. LOH of MCC was not f
The correlation between the mutation spectra of tumor suppressor genes Rb, p53, APC and MCC in human esophageal cancer (EC) and in human and monkey esophageal epithelium treated with ...N-Methyl-N-Benzyl nitrosamine (NMBzA) was studied using PCR amplification and direct sequencing methods. The results showed that in 40.9% (9/22) of the specimen examined, the mutation spectrum of p53 in primary EC was similar to that in the esophageal epithelium of human fetus (in vitro) and monkey (in vivo) treated with NMBzA. The same mutational spectra of tumor suppressor genes Rb, APC, MCC in esophageal epithelium cells of human and monkey treated with NMBzA were also found in some human primary EC. The correlation observed in the mutation spectra of multiple tumor suppressor genes between human primary EC and the esophageal epithelia of human and monkey origin treated with NMBzA wouldsuggest that NMBzA may be the esophageal etiological agent for human esophageal cancer in China.
To evaluate the role of APC, MCC and DCC genes in the development and progression of colorectal cancers, loss of heterozygosity (LOH) at these genetic loci was investigated in 41 surgically resected ...specimens of colorectal cancer by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. LOH at APC or/and MCC was detected in 38.9% (14/38) of the informative cases; at the APC in 28.0% (7/25) and at MCC locus in 36.4% (8/22). LOH at DCC genetic locus was detected in 55.3% (21/38) of the informative cases. LOH rates DCC gene in the cancer specimens with lymphnode metastasis (80.0%) and in Dukes' stage III and IV (71.4%) were significantly higher than that in specimens without lymphnode metastasis (39.1%) and in Dukes' stage I and II (35.3%) (P < 0.05). Our results suggest that LOH at APC/MCC and DCC is the common genetic alterations in colorectal cancer and DCC genetic LOH assay may be useful in predicting the prognosis of patients with colorectal cancer.
We have previously shown that the tumor suppressor gene for hepatocellular carcinoma (HCC) without cirrhosis may be located on chromosome 5q35-qter. In this study, we analyzed nine cases of primary ...HCC without cirrhosis using probes from the MCC and APC genes, which are in the region 5q21-22. None of the informative cases had allele loss detected by these probes, whereas the probe lambda MS8 for the region 5q35-qter showed allele loss in six out of six informative cases. The results confirm that the putative tumor suppressor gene for HCC without cirrhosis on chromosome 5q is distinct from the MCC and APC genes.
We have isolated several genes in the chromosome 5q21 region tightly linked to hereditary familial polyposis coli (FAP) and Gardner's syndrome (GS). Two of these genes (MCC and APC) were found to be ...somatically altered by point mutation, deletion or insertion in tumors of sporadic colorectal cancer patients. One of them (adenomatous polyposis coli; APC) was also found to mutate in the germ-line of both APC and GS patients. The identification of these genes has significant implications for understanding the pathogenesis of colorectal neoplasia and for the diagnosis and counseling of individuals with inherited predispositions to colorectal cancer. Furthermore, in one colon carcinoma, we identified an interesting mechanism causing dysfunction of the APC gene. This gene was disrupted by a somatic insertion of a long interspersed repetitive element (LINE-1 sequence: L1) into the last exon. As an insertional sequence contains a 3' portion of the L1 consensus sequence including the poly(A) tract and an 8 bp target-site duplication was observed, this insertion is suspected to be caused by a retrotranscriptional insertion of one of the L1 sequences. This is the first case of the disruption of a tumor suppressor gene by the insertion of a movable genetic element.
