Triple negative breast tumors: analysis of microsatellite instability

BRANHAM, M.T.; BELLINAUD V.; TELLO O; GAGO, F.E.; OROZCO, J.; VARGAS ROIG L.M.; ROQUÉ, M.

Mendoza

Conferencia; XLVIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2012

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Triple-negative (TN) breast cancers are defined as tumors that lack the expression of estrogen receptor (ER), progesterone receptor (PR), and HER2. TN tumors frequently express basal cytokeratins, EGF receptor, myoepithelial markers and rarely express E-cadherin. They are often p53 mutant and give evidence of genomic instability. The aim of this study was to evaluate instability within BAT-26 microsatellite and analyze copy number variations (CNV) and aberrant methylations in mismatch repair and tumor suppressor genes in TN tumors.  For copy number and methylation analysis we used the methyl specific multiplex ligation probe amplification assay (MS-MLPA). PCR amplification of BAT-26 was performed with specific primers and resolved by capillary electrophoresis. Forty five invasive ductal mammary carcinomas were collected in this study, including 27 TN tumors. We found that TN tumors exhibit significant microsatellite instability (MSI) (p<0.05) when compared with non-TN tumors. This instability was not associated with the methylation nor the deletion of MMR genes, but was significantly associated with aberrant methylation of tumor suppressor genes, i.e. DLC1 gene (p<0.05, phi =0.488) and APC gene (p<0.05, phi=0.486).  Here we show that TN tumors are BAT-26 unstable when compared with non-TN tumors. This instability is not associated with methylation nor deletion of MMR genes.