Implications of mismatch repair genes hMLH1 and hMSH2 in patients with sporadic renal cell carcinoma.
Objectives: To analyse the implications of DNA mismatch repair genes hMLH1 and hMSH2 in sporadic renal cell carcinoma (RCC).Materials and methods: Specimens of tumour and healthy renal tissue were collected from 89 patients treated for sporadic RCC. Another 95 blood samples taken from individuals wi...
| Autores: | ; ; ; ; ; ; ; |
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| Tipo de documento: | Artículo |
| Fecha de publicación: | 2008 |
| País: | España |
| Institución: | Universidad de Castilla-La Mancha |
| Repositorio: | RUIdeRA. Repositorio Institucional de la UCLM |
| OAI Identifier: | oai:ruidera.uclm.es:10578/34263 |
| Acceso en línea: | https://hdl.handle.net/10578/34263 |
| Nivel de acceso: | Acceso abierto |
| Palabra clave: | DNA methylation DNA mismatch repair genes Loss of heterozygosity Microsatellite instability RCC |
| _version_ | 1878735690701733888 |
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| author | Rubio del Campo, Antonio |
| author2 | Salinas Sánchez, Antonio Santiago Sánchez Sánchez, Francisco Giménez Bachs, José Miguel Donate Moreno, María José Pastor Navarro, Héctor Carrión López, Pedro Escribano Martínez, Julio |
| author2_role | author author author author author author author |
| author_browse | Carrión López, Pedro Donate Moreno, María José Escribano Martínez, Julio Giménez Bachs, José Miguel Pastor Navarro, Héctor Rubio del Campo, Antonio Salinas Sánchez, Antonio Santiago Sánchez Sánchez, Francisco |
| author_facet | Rubio del Campo, Antonio Salinas Sánchez, Antonio Santiago Sánchez Sánchez, Francisco Giménez Bachs, José Miguel Donate Moreno, María José Pastor Navarro, Héctor Carrión López, Pedro Escribano Martínez, Julio |
| author_role | author |
| collection | RUIdeRA. Repositorio Institucional de la UCLM |
| description | Objectives: To analyse the implications of DNA mismatch repair genes hMLH1 and hMSH2 in sporadic renal cell carcinoma (RCC).Materials and methods: Specimens of tumour and healthy renal tissue were collected from 89 patients treated for sporadic RCC. Another 95 blood samples taken from individuals with no history of cancer were also analysed. After DNA extraction and PCR amplification, microsatellite instability (MSI) was determined using the Bethesda microsatellite panel, two exonic microsatellites of the TGFbRII and BAX genes, and the microsatellite D3S1611. The promoter methylation status of hMLH1 was investigated using the HpaII and MspI restriction enzymes. In addition, a sequencing analysis of complete coding region of hMLH1 and hMSH2 genes was performed.Results: MSI and promoter hypermethylation of hMLH1 were not detected. Interestingly, loss of heterozygosity (LOH) was common among patients with RCC, particularly in microsatellite D3S1611 (34.9%). Mutations were identified in eight patients: K618A and V716M in gene hMLH1; and I145V, G322D, and the novel mutation P349A, in gene hMSH2. The mutations also appeared in healthy renal tissue and therefore, were considered as germline DNA sequence variations. There were G322D and K618A changes in >1% of the healthy control subjects, suggesting that they are DNA polymorphisms.Conclusions: Our data show that loss of function of both hMLH1 and hMSH2 is not involved in sporadic RCC, either by promoter methylation or mutation in their exons. However, LOH indicated that chromosomal instability affecting large fragments of DNA was the main genetic alteration we detected associated with RCC. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_81b61d861b3cef1d10f05bf2fa19691b |
| institution | Universidad de Castilla-La Mancha |
| instname_str | Universidad de Castilla-La Mancha |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:ruidera.uclm.es:10578/34263 |
| publishDate | 2008 |
| publishDateSort | 2008 |
| publisher | Wiley |
| publisherStr | Wiley |
| reponame_str | RUIdeRA. Repositorio Institucional de la UCLM |
| spelling | Implications of mismatch repair genes hMLH1 and hMSH2 in patients with sporadic renal cell carcinoma. Rubio del Campo, Antonio Salinas Sánchez, Antonio Santiago Sánchez Sánchez, Francisco Giménez Bachs, José Miguel Donate Moreno, María José Pastor Navarro, Héctor Carrión López, Pedro Escribano Martínez, Julio DNA methylation DNA mismatch repair genes Loss of heterozygosity Microsatellite instability RCC Objectives: To analyse the implications of DNA mismatch repair genes hMLH1 and hMSH2 in sporadic renal cell carcinoma (RCC).Materials and methods: Specimens of tumour and healthy renal tissue were collected from 89 patients treated for sporadic RCC. Another 95 blood samples taken from individuals with no history of cancer were also analysed. After DNA extraction and PCR amplification, microsatellite instability (MSI) was determined using the Bethesda microsatellite panel, two exonic microsatellites of the TGFbRII and BAX genes, and the microsatellite D3S1611. The promoter methylation status of hMLH1 was investigated using the HpaII and MspI restriction enzymes. In addition, a sequencing analysis of complete coding region of hMLH1 and hMSH2 genes was performed.Results: MSI and promoter hypermethylation of hMLH1 were not detected. Interestingly, loss of heterozygosity (LOH) was common among patients with RCC, particularly in microsatellite D3S1611 (34.9%). Mutations were identified in eight patients: K618A and V716M in gene hMLH1; and I145V, G322D, and the novel mutation P349A, in gene hMSH2. The mutations also appeared in healthy renal tissue and therefore, were considered as germline DNA sequence variations. There were G322D and K618A changes in >1% of the healthy control subjects, suggesting that they are DNA polymorphisms.Conclusions: Our data show that loss of function of both hMLH1 and hMSH2 is not involved in sporadic RCC, either by promoter methylation or mutation in their exons. However, LOH indicated that chromosomal instability affecting large fragments of DNA was the main genetic alteration we detected associated with RCC. Wiley https://hdl.handle.net/10578/34263 |
| spellingShingle | Implications of mismatch repair genes hMLH1 and hMSH2 in patients with sporadic renal cell carcinoma. Rubio del Campo, Antonio DNA methylation DNA mismatch repair genes Loss of heterozygosity Microsatellite instability RCC |
| title | Implications of mismatch repair genes hMLH1 and hMSH2 in patients with sporadic renal cell carcinoma. |
| title_full | Implications of mismatch repair genes hMLH1 and hMSH2 in patients with sporadic renal cell carcinoma. |
| title_fullStr | Implications of mismatch repair genes hMLH1 and hMSH2 in patients with sporadic renal cell carcinoma. |
| title_full_unstemmed | Implications of mismatch repair genes hMLH1 and hMSH2 in patients with sporadic renal cell carcinoma. |
| title_short | Implications of mismatch repair genes hMLH1 and hMSH2 in patients with sporadic renal cell carcinoma. |
| title_sort | Implications of mismatch repair genes hMLH1 and hMSH2 in patients with sporadic renal cell carcinoma. |
| topic | DNA methylation DNA mismatch repair genes Loss of heterozygosity Microsatellite instability RCC |
| topic_facet | DNA methylation DNA mismatch repair genes Loss of heterozygosity Microsatellite instability RCC |
| url | https://hdl.handle.net/10578/34263 |