دورية أكاديمية
In vivo interrogation of regulatory genomes reveals extensive quasi-insufficiency in cancer evolution
| العنوان: | In vivo interrogation of regulatory genomes reveals extensive quasi-insufficiency in cancer evolution |
|---|---|
| المؤلفون: | Fischer, Anja, Lersch, Robert, de Andrade Krätzig, Niklas, Strong, Alexander, Friedrich, Mathias J., Weber, Julia, Engleitner, Thomas, Öllinger, Rupert, Yen, Hsi Yu, Kohlhofer, Ursula, Gonzalez-Menendez, Irene, Sailer, David, Kogan, Liz, Lahnalampi, Mari, Laukkanen, Saara, Kaltenbacher, Thorsten, Klement, Christine, Rezaei, Majdaddin, Ammon, Tim, Montero, Juan J., Schneider, Günter, Mayerle, Julia, Heikenwälder, Mathias, Schmidt-Supprian, Marc, Quintanilla-Martinez, Leticia, Steiger, Katja, Liu, Pentao, Cadiñanos, Juan, Vassiliou, George S., Saur, Dieter, Lohi, Olli, Heinäniemi, Merja, Conte, Nathalie, Bradley, Allan, Rad, Lena, Rad, Roland |
| المساهمون: | Tampere University, Clinical Medicine, TAYS Cancer Centre, BioMediTech |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | 3111 Biomedicine, 3122 Cancers |
| الوصف: | In contrast to mono- or biallelic loss of tumor-suppressor function, effects of discrete gene dysregulations, as caused by non-coding (epi)genome alterations, are poorly understood. Here, by perturbing the regulatory genome in mice, we uncover pervasive roles of subtle gene expression variation in cancer evolution. Genome-wide screens characterizing 1,450 tumors revealed that such quasi-insufficiency is extensive across entities and displays diverse context dependencies, such as distinct cell-of-origin associations in T-ALL subtypes. We compile catalogs of non-coding regions linked to quasi-insufficiency, show their enrichment with human cancer risk variants, and provide functional insights by engineering regulatory alterations in mice. As such, kilo-/megabase deletions in a Bcl11b-linked non-coding region triggered aggressive malignancies, with allele-specific tumor spectra reflecting gradual gene dysregulations through modular and cell-type-specific enhancer activities. Our study constitutes a first survey toward a systems-level understanding of quasi-insufficiency in cancer and gives multifaceted insights into tumor evolution and the tissue-specific effects of non-coding mutations. ; Peer reviewed |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | fulltext |
| اللغة: | English |
| تدمد: | 2666-979X |
| العلاقة: | 100276; https://trepo.tuni.fi/handle/10024/146801Test; URN:NBN:fi:tuni-202303293268 |
| DOI: | 10.1016/j.xgen.2023.100276 |
| الإتاحة: | https://doi.org/10.1016/j.xgen.2023.100276Test https://trepo.tuni.fi/handle/10024/146801Test |
| حقوق: | cc by 4.0 ; openAccess |
| رقم الانضمام: | edsbas.6B35716E |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 2666979X |
|---|---|
| DOI: | 10.1016/j.xgen.2023.100276 |