Promoter hypermethylation of BRCA1 correlates with absence of expression in hereditary breast cancer tumors
| Autor: | Susan V. Smalley, Mauricio Camus, Paulina Kohen, Alejandro H. Corvalan, Pilar Carvallo, Manuel Alvarez, Alex Muñoz, Luigi Devoto, Paola Faundez, Luisa M. Solis, Teresa Tapia |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Cancer Research Heredity endocrine system diseases Molecular Sequence Data Breast Neoplasms Biology medicine.disease_cause Germline mutation Breast cancer medicine Humans Promoter Regions Genetic skin and connective tissue diseases Molecular Biology Gene Aged Base Sequence BRCA1 Protein Carcinoma Ductal Breast Methylation DNA Methylation Middle Aged medicine.disease Phenotype Gene Expression Regulation Neoplastic Hormone receptor DNA methylation Cancer research Female Carcinogenesis |
| Zdroj: | Epigenetics Artículos CONICYT CONICYT Chile instacron:CONICYT EPIGENETICS |
| ISSN: | 1559-2308 1559-2294 |
| DOI: | 10.4161/epi.3.3.6387 |
| Popis: | Germline mutations in BRCA1 account for a low proportion of hereditary cases in diverse populations. Several efforts have been made to find new genes involved in the inheritance of breast cancer with no success until today. The participation of BRCA1 in the development of breast cancer has been proposed in several studies where hypermethylation of its promoter and a decrease in expression has been reported for sporadic cases and one study on familial cases. To explore the participation of BRCA1 in hereditary carcinogenesis through a different mechanism than the inheritance of germline mutations, we studied the methylation status of its promoter in breast tumors, from patients previously screened for BRCA1/BRCA2 germline mutations. We also determined the presence of the BRCA1 protein in these tumors and correlated both events with tumor grade, hormone receptors and ERBB2 presence. Promoter hypermethylation of the BRCA1 gene was detected in 51% of our biopsies, among which 67% did not express the respective protein. This result leads us to suggest that hypermethylation could be considered as an inactivating mechanism for BRCA1 expression, either as a first or second hit. Moreover, a number of biopsies with absence of expression on BRCA1 showed negative detection of estrogen and progesterone receptors, a similar phenotype to BRCA1 mutated breast tumors. |
| Databáze: | OpenAIRE |
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