2026-04-17T21:39:06Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1780812025-12-05T09:23:47Zcom_2072_1057col_2072_478799col_2072_478908col_2072_478917

00925njm 22002777a 4500 dc Stefansson, Olafur A. author Moran, Sebastian author Gómez, Antonio author Sayols, Sergi author Arribas, Carles author Sandoval, Juan author Hilmarsdottir, Holmfridur author Olafsdottir, Elinborg author Tryggvadottir, Laufey author Jonasson, Jon G. author Eyfjord, Jorunn E. author Esteller, Manel author 2021-06-08T06:25:36Z 2021-06-08T06:25:36Z 2015-03-01 2021-06-08T06:25:36Z In cancer, epigenetic states are deregulated and thought to be of significance in cancer development and progression. We explored DNA methylation-based signatures in association with breast cancer subtypes to assess their impact on clinical presentation and patient prognosis. DNA methylation was analyzed using Infinium 450K arrays in 40 tumors and 17 normal breast samples, together with DNA copy number changes and subtype-specific markers by tissue microarrays. The identified methylation signatures were validated against a cohort of 212 tumors annotated for breast cancer subtypes by the PAM50 method (The Cancer Genome Atlas). Selected markers were pyrosequenced in an independent validation cohort of 310 tumors and analyzed with respect to survival, clinical stage and grade. The results demonstrate that DNA methylation patterns linked to the luminal-B subtype are characterized by CpG island promoter methylation events. In contrast, a large fraction of basal-like tumors are characterized by hypomethylation events occurring within the gene body. Based on these hallmark signatures, we defined two DNA methylation-based subtypes, Epi-LumB and Epi-Basal, and show that they are associated with unfavorable clinical parameters and reduced survival. Our data show that distinct mechanisms leading to changes in CpG methylation states are operative in different breast cancer subtypes. Importantly, we show that a few selected proxy markers can be used to detect the distinct DNA methylation-based subtypes thereby providing valuable information on disease prognosis. Càncer de mama Genètica ADN Metilació Breast cancer Genetics DNA Methylation A DNA methylation-based definition of biologically distinct breast cancer subtypes