Mutations of hMLH1 and hMSH2 in Patients With Suspected Hereditary Nonpolyposis Colorectal Cancer: Correlation With Microsatellite Instability and Abnormalities of Mismatch Repair Protein Expression
| العنوان: | Mutations of hMLH1 and hMSH2 in Patients With Suspected Hereditary Nonpolyposis Colorectal Cancer: Correlation With Microsatellite Instability and Abnormalities of Mismatch Repair Protein Expression |
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| المؤلفون: | Italo Bearzi, Mario Scartozzi, Emilio Porfiri, S. Rosati, Cristian Loretelli, Eva Galizia, Francesca Bianchi, Andrea Piga, Riccardo Cellerino, Annalisa Antolini |
| المصدر: | Journal of Clinical Oncology. 20:1203-1208 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2002. |
| سنة النشر: | 2002 |
| مصطلحات موضوعية: | Adult, Male, Oncology, congenital, hereditary, and neonatal diseases and abnormalities, Cancer Research, medicine.medical_specialty, Pathology, DNA Repair, Colorectal cancer, Gene mutation, medicine.disease_cause, Proto-Oncogene Proteins, Internal medicine, medicine, Humans, Missense mutation, neoplasms, Adaptor Proteins, Signal Transducing, Aged, Genetic testing, Mutation, medicine.diagnostic_test, business.industry, Nuclear Proteins, nutritional and metabolic diseases, Microsatellite instability, Mismatch Repair Protein, Middle Aged, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, Immunohistochemistry, digestive system diseases, Neoplasm Proteins, DNA-Binding Proteins, MutS Homolog 2 Protein, Female, DNA mismatch repair, Carrier Proteins, Colorectal Neoplasms, MutL Protein Homolog 1, business, Microsatellite Repeats |
| الوصف: | PURPOSE: The relationship between germ-line mutations of hMSH2 and hMLH1, microsatellite instability (MSI), and loss of DNA mismatch repair (MMR) gene expression were studied to formulate an effective selection protocol for patients with suspected hereditary nonpolyposis colorectal cancer who should be offered genetic testing. PATIENTS AND METHODS: Patients eligible for germ-line analysis of hMLH1 and hMSH2 were selected. Tumor specimens were obtained to assess MSI and loss of MMR gene expression. RESULTS: Among 37 patients who participated in the study, two hMSH2 and two hMLH1 missense mutations (11%) were detected, none of which was found in a panel of 60 healthy volunteers. High MSI was found in five tumors (19%) and low MSI in 10 tumors (39%); 12 tumors (46%) were microsatellite stable. Four tumors demonstrated loss of hMLH1, and three tumors demonstrated loss of hMSH2 protein expression. CONCLUSION: No relationship was found between MMR gene mutations and MSI; low or no MSI was found in the four patients with germ-line mutations, and none of the five patients with high MSI demonstrated abnormalities of MMR genes. On the contrary, loss of hMLH1 or hMSH2 expression was found in the tumors from three of the four patients demonstrating germ-line mutations. These data suggest that germ-line mutations of the MMR gene can occur in people with MSI-negative tumors. Sensitive clinical criteria and the study of MMR gene expression may be useful to identify this subset of patients. |
| تدمد: | 1527-7755 0732-183X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::88251153c0e84708e7e9c4297ad027f1Test https://doi.org/10.1200/jco.2002.20.5.1203Test |
| رقم الانضمام: | edsair.doi.dedup.....88251153c0e84708e7e9c4297ad027f1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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