AIM: To define the common deleted region on the long arm of haman chromosome 7q linked to primary gastric carcinomas in Chinese by loss of heterozygosity (LOH) and its clinical significance.

METHODS: Nine microsatellite markers distributed over chromosome 7q with an average marker density of 10cM were used to examine 70 primary gastric carcinomas for LOH by PCR amplification. The PCR products were separated by electrophoresis on polyacrylamide gel. Genescan and Genotyper softwares were used to analyze LOH.

RESULTS: LOH with at least one marker on 7q occurred in 34.3% (12/50) of the tumors. Among them, LOH at D7S486 and D7S798 was higher in 24.0% (24/70) and 19.2% (5/26), respectively. By statistical analysis we also observed an obvious genotype-phenotype correlation on 7q (P < 0.05). The frequency of LOH at D7S486 in patients with lymph node metastasis was significantly higher than that in those without lymph node metastasis (P = 0.015).

CONCLUSION: The high incidence of LOH at D7S486 and its correlation with poorer prognosis suggest that there might be putative tumor suppressor genes in this region involved in the tumorigenesis and progression of gastric carcinoma.

• LOH
• Chromosome 7
• Gastric cancer

• Adult
• Aged
• Chromosomes, Human, Pair 7/genetics
• Female
• Genetic Linkage
• Humans
• Loss of Heterozygosity
• Male
• Microsatellite Repeats
• Middle Aged
• Stomach Neoplasms/genetics

AIM: To verify the effectiveness of denaturing high-performance liquid chromatography (DHPLC) in detecting somatic mutation of p53 gene in gastric carcinoma tissues. The superiority of this method has been proved in the detection of germline mutations, but it was not very affirmative with respect to somatic mutations in tumor specimens. ST7 gene, a candidate tumor suppressor gene identified recently at human chromosome 7q31.1, was also detected because LOH at this site has also been widely reported in stomach cancer.

METHODS: DNA was extracted from 39 cases of surgical gastric carcinoma specimen and their correspondent normal mucosa. Seven fragments spanning the 11 exons were used to detect the mutation of p53 gene and the four exons reported to have mutations in ST7 gene were amplified by PCR and directly analyzed by DHPLC without mixing with wild-type allele.

RESULTS: In the analysis of p53 gene mutation, 9 aberrant DHPLC chromatographies were found in tumor tissues, while their normal-adjacent counterparts running in parallel showed a normal shape. Subsequent sequencing revealed nine sequence variations, 1 polymorphism and 8 mutations including 3 mutations not reported before. The mutation rate of p53 gene (21%) was consistent with that previously reported. Furthermore, no additional aberrant chromatography was found when wild-type DNA was added into the DNA of other 30 tumor samples that showed normal shapes previously. The positivity of p53 mutations was significantly higher in intestinal-type carcinomas (40%) than that in diffuse-type (8.33%) carcinomas of the stomach. No mutation of ST7 gene was found.

CONCLUSION: DHPLC is a very convenient method for the detection of somatic mutations in gastric carcinoma. The amount of wild type alleles supplied by the non-tumorous cells in gastric tumor specimens is enough to form heteroduplex with mutant alleles for DHPLC detection. ST7 gene may not be the target gene of inactivation at 7q31 site in gastric carcinoma.

• Base Sequence
• Chromatography, High Pressure Liquid/methods
• Chromosomes, Human, Pair 7
• DNA, Neoplasm/chemistry
• DNA, Neoplasm/genetics
• Genes, Tumor Suppressor
• Genes, p53
• Germ-Line Mutation
• Humans
• Membrane Proteins/genetics
• Mutation
• Polymerase Chain Reaction
• Sensitivity and Specificity
• Stomach Neoplasms/genetics
• Stomach Neoplasms/pathology
• Tumor Suppressor Protein p53/genetics