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Supplementary Table S19 from A Functional Survey of the Regulatory Landscape of Estrogen Receptor–Positive Breast Cancer Evolution

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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 S19: Overlap between regions with excess of functional alterations. The regions considered in these overlaps are highlighted in table S13.1. S19.1: overlap with noncoding drivers identified by PCAWG (as listed in Supplementary Table 5 of Rheinbay et al. 2020). S19.2: overlap with regulatory mutations from breast cancer samples, as identified by HMF (as listed in Supplementary Table 5 of Dietlein et al. 2022). S19.3: overlap with noncoding mutational hotspots identified by HMF (as listed in Supplementary Table 21 of Dietlein et al. 2022). S19.4: overlap with genes associated with mutation events in non-coding regions from previous studies, as annotated by HMF (as listed in Supplementary Table 22 of Dietlein et al. 2022).

Funding

Cancer Research UK (CRUK)

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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.