Sofia, MasuelliSebastian, RealEmanuel, CampoyBranham, Maria TeresitaMatias Marzese, DiegoMatthew, SalomonDe Blas, GerardoRodolfo, AriasMichael, LevinMaria, Roque2024-10-042024-10-042022-12Sofia M, Sebastian R, Emanuel C, Branham MT, Marzese DM, Matthew S, et al. When left does not seem right: epigenetic and bioelectric differences between left- and right-sided breast cancer. Mol Med. 2022 Dec;28(1):15.1076-1551https://hdl.handle.net/20.500.13003/19912https://hdl.handle.net/20.500.12105/23561Background: During embryogenesis lateral symmetry is broken, giving rise to Left/Right (L/R) breast tissues with distinct identity. L/R-sided breast tumors exhibit consistently-biased incidence, gene expression, and DNA methylation. We postulate that a differential L/R tumor-microenvironment crosstalk generates different tumorigenesis mechanisms. Methods: We performed in-silico analyses on breast tumors of public datasets, developed xenografted tumors, and conditioned MDA-MB-231 cells with L/R mammary extracts. Results: We found L/R differential DNA methylation involved in embryogenic and neuron-like functions. Focusing on ion-channels, we discovered significant L/R epigenetic and bioelectric differences. Specifically, L-sided cells presented increased methylation of hyperpolarizing ion channel genes and increased Ca2+ concentration and depolarized membrane potential, compared to R-ones. Functional consequences were associated with increased proliferation in left tumors, assessed by KI67 expression and mitotic count. Conclusions: Our findings reveal considerable L/R asymmetry in cancer processes, and suggest specific L/R epigenetic and bioelectric differences as future targets for cancer therapeutic approaches in the breast and many other paired organs.enghttp://creativecommons.org/licenses/by/4.0/AsymmetryLateralityLeftRightBreast cancerElectric ImpedanceDNA MethylationComputational BiologyHumansCell Line, TumorEpigenesis, GeneticTranscriptomeTumor MicroenvironmentFemaleAnimalsUnilateral Breast NeoplasmsGene Expression Regulation, NeoplasticMiceresearch articleAttribution 4.0 International351234132811510.1186/s10020-022-00440-51528-3658Molecular Medicineopen accessAnimalesLínea Celular TumoralEpigénesis GenéticaRegulación Neoplásica de la Expresión GénicaFemeninoNeoplasias de Mama UnilateralesHumanosMetilación de ADNImpedancia EléctricaBiología ComputacionalRatonesTranscriptomaMicroambiente Tumoral2-s2.0-85124232371751622300004L2014948285