Methylation profile of triple negative breast carcinomas

BRANHAM MARIA TERESITA; MARZESE DIEGO; LAURITO SERGIO; GAGO FRANCISCO; OROZCO JAVIER; TELLO OLGA; VARGAS ROIG LAURA; ROQUÉ MARIA

Oncogenesis

Nature Publishing Group

Año: 2012 p. 1 - 7

2157-9024

Breast cancer is a group of clinically, histopathologically and molecularly heterogeneous diseases, with different outcomes and responses to treatment. Triple-negative breast cancers are defined as tumors that lack the expression of estrogen receptor (ER), progesterone receptor (PR), and HER2. This subgroup accounts for 15% of all types of breast cancer and its prevalence is higher among young African, African-American and Latino women. The hypermethylation of CpG islands (CpGI) is a common epigenetic alteration for suppressing gene expression in breast cancer and has been shown to be a key factor in breast carcinogenesis.  In this study we analyzed the hypermethylation of 110 GpGI whitin 69 cancer related genes in TN tumors.  For the methylation analysis, we used the methyl specific-multiplex ligation probe amplification assay. We found that the number of methylated CpGI is similar between TN and non-TN tumors, but the methylated genes between the groups are different. The methylation profile of TN tumors is defined by the methylation of 5 genes: i.e. CDKN2B, CD44, MGMT, RB and p73 plus the non-methylation of 11 genes, i.e. GSTP1, PMS2, MSH2, MLH1, MSH3, MSH6, DLC1, CACNA1A, CACNA1G, TWIST1 and ID4. We conclude that TN tumors have a specific methylation profile.  Our findings give new information for better understanding tumor etiology and encourage future studies on potential drug targets for Triple Negative breast tumors, which now lack of a specific treatment.