Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Epigenetic regulation of ID4 in the determination of the BRCAness phenotype in breast cancer. Breast Cancer Res Treat 2016 Jan;155(1):13-23 PMID: 26610810 PMCID: PMC6036618

Pubmed ID

26610810

DOI

10.1007/s10549-015-3648-0

Abstract

BRCAness breast tumors represent a group of sporadic tumors characterized by a reduction in BRCA1 gene expression. As BRCA1 is involved in double-strand breaks (DSBs) repair, dysfunctional BRCA pathway could make a tumor sensitive to DNA damaging drugs (e.g., platinum agents). Thus, accurately identifying BRCAness could contribute to therapeutic decision making in patients harboring these tumors. The purpose of this study was to identify if BRCAness tumors present a characteristic methylation profile and/or were related to specific clinico-pathological features. BRCAness was measured by MLPA in 63 breast tumors; methylation status of 98 CpG sites within 84 cancer-related genes was analyzed by MS-MLPA. Protein and mRNA expressions of the selected genes were measured by quantitative real-time PCR and Western Blot. BRCAness was associated with younger age, higher nuclear pleomorphism, and triple-negative (TN) status. Epigenetically, we found that the strongest predictors for BRCAness tumors were the methylations of MLH1 and PAX5 plus the unmethylations of CCND2 and ID4. We determined that ID4 unmethylation correlated with the expression levels of both its mRNA and protein. We observed an inverse relation between the expressions of ID4 and BRCA1. To the best of our knowledge, this is the first report suggesting an epigenetic regulation of ID4 in BRCAness tumors. Our findings give new information of BRCAness etiology and encourage future studies on potential drug targets for BRCAness breast tumors.

Author List

Branham MT, Campoy E, Laurito S, Branham R, Urrutia G, Orozco J, Gago F, Urrutia R, Roqué M

Author

Raul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin




Scopus

2-s2.0-84953357119   6 Citations

MESH terms used to index this publication - Major topics in bold

Adult
Biomarkers, Tumor
Breast Neoplasms
Carcinoma, Ductal, Breast
CpG Islands
DNA Methylation
DNA Modification Methylases
DNA Repair Enzymes
Epigenesis, Genetic
Epigenomics
Female
Gene Amplification
Gene Expression Regulation, Neoplastic
Genes, BRCA1
Genes, BRCA2
Humans
Inhibitor of Differentiation Proteins
Middle Aged
Neoplasm Grading
Neoplasm Staging
Phenotype
Tumor Suppressor Proteins
Young Adult
jenkins-FCD Prod-332 f92a19b0ec5e8e1eff783fac390ec127e367c2b5