dataset
posted on 2024-09-04, 07:41 authored by Iros Barozzi, Neil Slaven, Eleonora Canale, Rui Lopes, Inês Amorim Monteiro Barbosa, Melusine Bleu, Diana Ivanoiu, Claudia Pacini, Emanuela Mensa’, Alfie Chambers, Sara Bravaccini, Sara Ravaioli, Balázs Győrffy, Maria Vittoria Dieci, Giancarlo Pruneri, Giorgio Giacomo Galli, Luca Magnani Supplementary Table S14: Datasets used for the training of the TF-specific deltaSVM models. For each TF, the corresponding gene symbol, along with information about the cells from which the ChIP-seq binding profile was obtained, the treatment the cells were exposed to (if any), and reference to the corresponding records on the Gene Expression Omnibus, are indicated. Information about the matched, high-quality position weight matrix (PWM) utilized as source of information to infer the binding affinities of each TF is also provided. For each PWM, an identifier is indicated, along with the corresponding reference database or publication (including Pubmed ID).
Funding
Cancer Research UK (CRUK)
History
ARTICLE ABSTRACT
Only a handful of somatic alterations have been linked to endocrine therapy resistance in hormone-dependent breast cancer, potentially explaining ∼40% of relapses. If other mechanisms underlie the evolution of hormone-dependent breast cancer under adjuvant therapy is currently unknown. In this work, we employ functional genomics to dissect the contribution of cis-regulatory elements (CRE) to cancer evolution by focusing on 12 megabases of noncoding DNA, including clonal enhancers, gene promoters, and boundaries of topologically associating domains. Parallel epigenetic perturbation (CRISPRi) in vitro reveals context-dependent roles for many of these CREs, with a specific impact on dormancy entrance and endocrine therapy resistance. Profiling of CRE somatic alterations in a unique, longitudinal cohort of patients treated with endocrine therapies identifies a limited set of noncoding changes potentially involved in therapy resistance. Overall, our data uncover how endocrine therapies trigger the emergence of transient features which could ultimately be exploited to hinder the adaptive process.Significance: This study shows that cells adapting to endocrine therapies undergo changes in the usage or regulatory regions. Dormant cells are less vulnerable to regulatory perturbation but gain transient dependencies which can be exploited to decrease the formation of dormant persisters.
