AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions. METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gast...AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions. METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gastric cancer, intestinal metaplasia, atrophic gastritis, and atypical hyperplasia were analyzed for PTEN LOH and mutations within the entire coding region of PTEN gene by PCR-SSCP denaturing PAGE gel electrophoresis, and PTEN mutation was detected by PCR-SSCP sequencing followed by silver staining. RESULTS: LOH rate found in respectively atrophic gastritis was 10% (3/30), intestinal metaplasia 10% (3/30), atypical hyperplasia 13.3% (4/30), early stage gastric cancer 20% (6/30), and advanced stage gastric cancer 33.3% (9/30), None of the precancerous lesions and early stage gastric cancer showed PTEN mutations, but 10% (3/30) of the advanced stage gastric cancers, which were all positive for LOH, showed PTEN mutation. CONCLUSION: LOH of PTEN gene appears in precancerous lesions, and PTEN mutations are restricted to advanced gastric cancer, LOH and mutation of PTEN gene are closely related to the infiltration and metastasis of gastric cancer.展开更多
A small proportion of many cancers are due to inherited mutations in genes,which result in a high risk to the indi-vidual of developing specific cancers. There are several classes of genes that may be involved: tumour...A small proportion of many cancers are due to inherited mutations in genes,which result in a high risk to the indi-vidual of developing specific cancers. There are several classes of genes that may be involved: tumour suppressor genes,onco-genes,genes encoding proteins involved in DNA repair and cell cycle control,and genes involved in stimulating the angiogenic pathway. Alterations in susceptibility to cancer may also be due to variations in genes involved in carcinogen metabolism. This review discusses examples of some of these genes and the associated clinical conditions caused by the inheritance of mutations in such genes.展开更多
The short report will be focused on the genetic basis and possible mechanisms of tumorigenesis, common types of cancer, the importance of genetic diagnosis of cancer, and the methodology of cancer genetic diagnosis. T...The short report will be focused on the genetic basis and possible mechanisms of tumorigenesis, common types of cancer, the importance of genetic diagnosis of cancer, and the methodology of cancer genetic diagnosis. They will also review presymptomatic testing of hereditary cancers, and the application of expression profiling to identify patients likely to benefit from particular therapeutic approaches.展开更多
The tumor suppressor p53 is one of the most frequently mutated genes in human cancers. MicroRNAs （miRNAs） are small non-protein coding RNAs that regulate gene expression on the post-transcriptional level. Recently, ...The tumor suppressor p53 is one of the most frequently mutated genes in human cancers. MicroRNAs （miRNAs） are small non-protein coding RNAs that regulate gene expression on the post-transcriptional level. Recently, it was shown that p53 regulates the expression of several miRNAs, thereby representing an important mechanism of p53 signaling. Several independent studies identified the members of the miR-34 family as the most prevalent p53-induced miRNAs, miR-34s are frequently silenced in variety of tumor entities, suggesting that they are important tumor suppressors. Indeed, ectopic expression of miR-34s inhibits proliferation, epithelial to mes- enchymat transition, migration, invasion, and metastasis of various cancer celt entities. Moreover, delivery or re-expression of miR-34 leads to notable repression of tumor growth and metastasis in cancer mouse models, and may therefore represent an efficient strategy for future cancer therapeutics. Besides their crucial functions in cancer, members of the miR-34 family also play important roles in spermatogenesis, stem cell differentiation, neuronal development, aging, and cardiovascular functions. Consequently, miR-34 has also been implicated in various non-cancerous diseases, such as brain disorders, osteoporosis, and cardiovascular complications.展开更多
基金Supported by the National Natural Science Foundation of China,No. 30070845
文摘AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions. METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gastric cancer, intestinal metaplasia, atrophic gastritis, and atypical hyperplasia were analyzed for PTEN LOH and mutations within the entire coding region of PTEN gene by PCR-SSCP denaturing PAGE gel electrophoresis, and PTEN mutation was detected by PCR-SSCP sequencing followed by silver staining. RESULTS: LOH rate found in respectively atrophic gastritis was 10% (3/30), intestinal metaplasia 10% (3/30), atypical hyperplasia 13.3% (4/30), early stage gastric cancer 20% (6/30), and advanced stage gastric cancer 33.3% (9/30), None of the precancerous lesions and early stage gastric cancer showed PTEN mutations, but 10% (3/30) of the advanced stage gastric cancers, which were all positive for LOH, showed PTEN mutation. CONCLUSION: LOH of PTEN gene appears in precancerous lesions, and PTEN mutations are restricted to advanced gastric cancer, LOH and mutation of PTEN gene are closely related to the infiltration and metastasis of gastric cancer.
文摘A small proportion of many cancers are due to inherited mutations in genes,which result in a high risk to the indi-vidual of developing specific cancers. There are several classes of genes that may be involved: tumour suppressor genes,onco-genes,genes encoding proteins involved in DNA repair and cell cycle control,and genes involved in stimulating the angiogenic pathway. Alterations in susceptibility to cancer may also be due to variations in genes involved in carcinogen metabolism. This review discusses examples of some of these genes and the associated clinical conditions caused by the inheritance of mutations in such genes.
文摘The short report will be focused on the genetic basis and possible mechanisms of tumorigenesis, common types of cancer, the importance of genetic diagnosis of cancer, and the methodology of cancer genetic diagnosis. They will also review presymptomatic testing of hereditary cancers, and the application of expression profiling to identify patients likely to benefit from particular therapeutic approaches.
文摘The tumor suppressor p53 is one of the most frequently mutated genes in human cancers. MicroRNAs （miRNAs） are small non-protein coding RNAs that regulate gene expression on the post-transcriptional level. Recently, it was shown that p53 regulates the expression of several miRNAs, thereby representing an important mechanism of p53 signaling. Several independent studies identified the members of the miR-34 family as the most prevalent p53-induced miRNAs, miR-34s are frequently silenced in variety of tumor entities, suggesting that they are important tumor suppressors. Indeed, ectopic expression of miR-34s inhibits proliferation, epithelial to mes- enchymat transition, migration, invasion, and metastasis of various cancer celt entities. Moreover, delivery or re-expression of miR-34 leads to notable repression of tumor growth and metastasis in cancer mouse models, and may therefore represent an efficient strategy for future cancer therapeutics. Besides their crucial functions in cancer, members of the miR-34 family also play important roles in spermatogenesis, stem cell differentiation, neuronal development, aging, and cardiovascular functions. Consequently, miR-34 has also been implicated in various non-cancerous diseases, such as brain disorders, osteoporosis, and cardiovascular complications.
