Cell signaling events differentiate ER-negative subtypes from ER-positive breast cancer

• Published in: Medical oncology (Northwood, London, England) London, England), 2015-05, Vol.32 (5), p.142-142, Article 142
• Main Authors: Worsham, Maria J., Chitale, Dhanajay, Chen, Kang Mei, Datta, Indrani, Divine, George
• Format: Article
• Language: English
• Subjects: Biomarkers, Tumor - genetics; Breast cancer; Breast Neoplasms - genetics; Female; Hematology; Humans; Internal Medicine; Medicine; Medicine & Public Health; Methylation; Oncology; Original Paper; Pathology; Receptor, ErbB-2 - genetics; Signal Transduction - genetics
• ISSN: 1357-0560; 1559-131X
• DOI: 10.1007/s12032-015-0565-3

Currently available markers routinely used in clinical practice are of limited value to patients with estrogen receptor-negative (ER − ) breast cancer [basal-like and HER2neu-positive (HER + )], an aggressive subtype. Our aim was to uncover molecular pathways and signaling networks exposed by differentially methylated genes informative of the biology of ER − breast cancer (BC) subtypes versus ER-positive (ER + ). Whole-genome methylation array analysis was carried out using the Illumina Infinium HumanMethylation27 BeadChip on 14 primary BC: five ER + , four triple-negative (TNBC), and five ER − HER2 + . Degree of methylation was calculated as a β -value (ranging from 0 to 1), and M -values [log ( β /(1 −  β )] were used for significance tests. To identify methylated genes associated with ER − subtypes (TNBC and ER − HER2 + ) and distinct from ER + , a weighted algorithm, developed to increase statistical rigor, called out genes in which methylation changed dramatically between ER + and ER − subtypes. Differentially methylated gene lists examined using Ingenuity Pathway Analysis called out canonical pathways and networks with clues to biological distinctiveness as well as relatedness between ER − subtypes as compared to ER + BC. The study highlights the interplay of ER − subtype-specific genes and their signaling pathways as potential putative fingerprints in refining classification of BC subtypes and as potential biological markers designed to hit multiple targets.