INSTITUTO ARGENTINO DE NIVOLOGIA, GLACIOLOGIA Y CIENCIAS AMBIENTALES
Unidad Ejecutora - UE
Epigenetic regulation of ID4 in the determination of the BRCAness phenotype in breast cancer
BRANHAM, MARIA T.; CAMPOY, E. ; LAURITO, S.; BRANHAM, RICHARD L. JR.; URRITIA, G.; OROZCO, J.; GAGO, F.; URRITIA, R.; ROQUE, M.
BREAST CANCER RESEARCH AND TREATMENT
Lugar: Berlin; Año: 2015
BRCAness breast tumors represent a group ofsporadic tumors characterized by a reduction in BRCA1gene expression. As BRCA1 is involved in double-strandbreaks (DSBs) repair, dysfunctional BRCA pathway couldmake a tumor sensitive to DNA damaging drugs (e.g.,platinum agents). Thus, accurately identifying BRCAnesscould contribute to therapeutic decision making in patientsharboring these tumors. The purpose of this study was toidentify if BRCAness tumors present a characteristicmethylation profile and/or were related to specific clinicopathologicalfeatures. BRCAness was measured by MLPAin 63 breast tumors; methylation status of 98 CpG siteswithin 84 cancer-related genes was analyzed by MSMLPA.Protein and mRNA expressions of the selectedgenes were measured by quantitative real-time PCR andWestern Blot. BRCAness was associated with younger age,higher nuclear pleomorfism, and triple-negative (TN) status.Epigenetically, we found that the strongest predictorsfor BRCAness tumors were the methylations of MLH1 andPAX5 plus the unmethylations of CCND2 and ID4. Wedetermined that ID4 unmethylation correlated with theexpression levels of both its mRNA and protein. Weobserved an inverse relation between the expressions ofID4 and BRCA1. To the best of our knowledge, this is thefirst report suggesting an epigenetic regulation of ID4 inBRCAness tumors. Our findings give new information ofBRCAness etiology and encourage future studies onpotential drug targets for BRCAness breast tumors.