Characterization of mutator pathway in younger-age-onset colorectal adenocarcinomas
| العنوان: | Characterization of mutator pathway in younger-age-onset colorectal adenocarcinomas |
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| المؤلفون: | Jin Cheon Kim, Jung Seon Kim, Seon Ae Roh, Hee Cheol Kim |
| المصدر: | Journal of Korean Medical Science |
| بيانات النشر: | Korean Academy of Medical Sciences, 2003. |
| سنة النشر: | 2003 |
| مصطلحات موضوعية: | Adult, Male, congenital, hereditary, and neonatal diseases and abnormalities, DNA Repair, Colorectal cancer, DNA repair, Mutation, Missense, Biology, Adenocarcinoma, Proto-Oncogene Proteins, medicine, Missense mutation, Humans, Epigenetics, Prospective Studies, Registries, Age of Onset, Promoter Regions, Genetic, neoplasms, Adaptor Proteins, Signal Transducing, Genetics, Microsatellite instability, nutritional and metabolic diseases, Nuclear Proteins, Proteins, General Medicine, DNA Methylation, medicine.disease, digestive system diseases, Neoplasm Proteins, DNA-Binding Proteins, MutS Homolog 2 Protein, DNA methylation, Cancer research, DNA mismatch repair, Female, Carrier Proteins, Colorectal Neoplasms, MutL Protein Homolog 1, Research Article, Microsatellite Repeats |
| الوصف: | The high-frequency microsatellite instability (MSI-H) phenotype, frequently identified in hereditary nonpolyposis colorectal cancer (HNPCC), also accounts for approximately 15% of sporadic colorectal cancers. Microsatellite instability (MSI) occurs from the mutational inactivation of the DNA mismatch repair genes, i.e. hMSH2 and hMLH1 in HNPCC, as well as from epigenetic inactivation of hMLH1 in sporadic colorectal tumors. The mutator pathway including microsatellite instability, hMLH1 promoter methylation, and hMSH2 and hMLH1 mutation patterns were identified in 21 sporadic colorectal adenocarcinoma patients younger than 30 yr excluding HNPCC. More than half of tumors showed MSI, with five MSI-H and six MSI-L (low-frequency microsatellite instability). Three of six MSI-H tumors showed the hMLH1 promoter methylation and did not express the hMLH1 protein. On the other hand, all MSI-L and all MSS (microsatellite stable) tumors expressed both hMSH2 and hMLH1 proteins. Two novel mutations, i.e. a missense mutation in hMLH1 and a splice-site alteration in hMSH2, were identified in two patients respectively. Although mutator pathway was implicated in younger-age-onset colorectal carcinogenesis, many tumors appeared to evolve from different genetic events other than hMSH2 and hMLH1 mutations frequently identified in HNPCC. |
| اللغة: | English |
| تدمد: | 1598-6357 1011-8934 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::adaa70e046905268c1bd91f3d95f41c2Test http://europepmc.org/articles/PMC3055043Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....adaa70e046905268c1bd91f3d95f41c2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15986357 10118934 |
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