Patrón de metilación génico en el cáncer de mama

• Juan Carlos Roa S ^[1] ; Leonardo Anabalón R ^[1] ; Oscar Tapia E ^[1] ; Javier Martínez S ^[1] ; Juan Carlos Araya O ^[1] ; Miguel Villaseca H ^[1] ; Pablo Guzmán G ^[1] ; Iván Roa E ^[1]
  1. [1] Universidad de La Frontera

     Universidad de La Frontera

     Temuco, Chile

     
• Localización: Revista Médica de Chile, ISSN-e 0034-9887, Vol. 132, Nº. 9, 2004, págs. 1069-1077
• Idioma: español
• Títulos paralelos:
  • Promoter methylation profile in breast cancer
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• Resumen

  • Background: Genomic DNA methylation, mutations and allelic deletions explain the inactivation of genes involved in cell proliferation and cell cycle control mechanisms. Aim: To analyze the methylation pattern of important genes related to different carcinogenic mechanisms in patients with breast cancer and the relationship with its biological behavior. Material and methods: Seventy fresh-frozen breast cancer samples were selected. The methylation specific PCR (MSP) test was used to analyze promoter methylation status for genes CDKN2A (p16), hMLH1, APC, CDH1 (Cadherin E) and FHIT. Results: We found methylation in at least one of the genes studied in 88% of cases and in 3 or more genes in 40.5% of cases. The frequencies of promoter hypermethylation of CDKN2A, hMLH1, APC, CDH1 and FHIT were 41.4%, 11.4%, 52.9%, 70% y 42.9%, respectively. We found a relationship between CDKN2A methylation and better survival (p=0.002). CDH1 methylation and poor histological differentiation (p=0.007), hMLH1 methylation and non-Mapuche ethnicity (p=0.03), APC methylation and larger tumor size (p <0.05), FHIT methylation and lack of estrogen receptor IHC expression (p <0.05). Conclusions: The high frequency of promoter methylation in patients with breast cancer confirms its role in breast carcinogenesis. The finding of alterations in the methylation pattern of genes studied and its association with prognostic factors is a helpful tool in the search of new criteria for clinical and therapeutic decision making (Rev Méd Chile 2004; 132: 1069-77)