title: Cell signaling events differentiate ER-negative subtypes from ER-positive breast cancer.
abstract: 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.
authors: Department of Otolaryngology, Henry Ford Hospital, 1Ford Place, 1D, Detroit, MI, 48202, USA, mworsha1@hfhs.org.
authors: Maria J
authors: MJ
authors: Worsham
authors: Dhanajay
authors: D
authors: Chitale
authors: Kang Mei
authors: KM
authors: Chen
authors: Indrani
authors: I
authors: Datta
authors: George
authors: G
authors: Divine
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D008745:Methylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases