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@article{Magnani:2022:rs.3.rs-1432636/v1,
author = {Magnani, L},
doi = {rs.3.rs-1432636/v1},
title = {Genetic and epigenetic driven variation in regulatory regions activity contribute to adaptation and evolution under endocrine treatment},
url = {http://dx.doi.org/10.21203/rs.3.rs-1432636/v1},
year = {2022}
}

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TY  - JOUR
AB  - <jats:title>Abstract</jats:title>        <jats:p>Comprehensive profiling of hormone-dependent breast cancer (HDBC) has identified hundreds of protein-coding alterations contributing to cancer initiation1,2, but only a handful have been linked to endocrine therapy resistance, potentially contributing to 40% of relapses1,3–9. If other mechanisms underlie the evolution of HDBC under adjuvant therapy is currently unknown. In this work, we employ integrative functional genomics to dissect the contribution of cis-regulatory elements (CREs) to cancer evolution by focusing on 12 megabases of non-coding DNA, including clonal enhancers10, gene promoters, and boundaries of topologically associating domains11. Massive parallel perturbation in vitro reveals context-dependent roles for many of these CREs, with a specific impact on dormancy entrance12,13 and endocrine therapy resistance9. Profiling of CRE somatic alterations in a unique, longitudinal cohort of patients treated with endocrine therapies identifies non-coding changes involved in therapy resistance. Overall, our data uncover actionable transient transcriptional programs critical for dormant persister cells and unveil new regulatory nodes driving evolutionary trajectories towards disease progression</jats:p>
AU  - Magnani,L
DO  - rs.3.rs-1432636/v1
PY  - 2022///
TI  - Genetic and epigenetic driven variation in regulatory regions activity contribute to adaptation and evolution under endocrine treatment
UR  - http://dx.doi.org/10.21203/rs.3.rs-1432636/v1
ER  -

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