Structure, Dynamics, and Impact of Replication Stress–Induced Structural Variants in Hepatocellular Carcinoma
| العنوان: | Structure, Dynamics, and Impact of Replication Stress–Induced Structural Variants in Hepatocellular Carcinoma |
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| المؤلفون: | Quentin Bayard, Pierre Cordier, Camille Péneau, Sandrine Imbeaud, Theo Z. Hirsch, Victor Renault, Jean-Charles Nault, Jean-Frédéric Blanc, Julien Calderaro, Chantal Desdouets, Jessica Zucman-Rossi, Eric Letouzé |
| المساهمون: | Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Fondation Jean Dausset CEPH, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Formation et de Recherche Santé, Médecine, Biologie Humaine [Bobigny], Université Paris 13 (UP13)-Sorbonne Paris Cité, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Henri Mondor, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Zucman-Rossi, Jessica |
| المصدر: | Cancer Research Cancer Research, American Association for Cancer Research, 2022, 82 (8), pp.1470-1481. ⟨10.1158/0008-5472.CAN-21-3665⟩ Cancer Research, 2022, 82 (8), pp.1470-1481. ⟨10.1158/0008-5472.CAN-21-3665⟩ |
| بيانات النشر: | American Association for Cancer Research (AACR), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, Carcinoma, Hepatocellular, Whole Genome Sequencing, Oncology, Cyclins, Liver Neoplasms, Humans, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Oncogenes, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology |
| الوصف: | Oncogene activation leads to replication stress and promotes genomic instability. Here we combine optical mapping and whole-genome sequencing (WGS) to explore in depth the nature of structural variants (SV) induced by replication stress in cyclin-activated hepatocellular carcinomas (CCN-HCC). In addition to classical tandem duplications, CCN-HCC displayed frequent intra-chromosomal and interchromosomal templated insertion cycles (TIC), likely resulting from template switching events. Template switching preferentially involves active topologically associated domains that are proximal to one another within the 3D genome. Template sizes depend on the type of cyclin activation and are coordinated within each TIC. Replication stress induced continuous accumulation of SVs during CCN-HCC progression, fostering the acquisition of new driver alterations and large-scale copy-number changes at TIC borders. Together, this analysis sheds light on the mechanisms, dynamics, and consequences of SV accumulation in tumors with oncogene-induced replication stress. Significance: Optical mapping and whole-genome sequencing integration unravels a unique signature of replication stress–induced structural variants that drive genomic evolution and the acquisition of driver events in CCN-HCC. |
| وصف الملف: | application/pdf |
| تدمد: | 1538-7445 0008-5472 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::94a592b2955c121f211fc9d610f3d3b4 https://doi.org/10.1158/0008-5472.can-21-3665 |
| حقوق: | EMBARGO |
| رقم الأكسشن: | edsair.doi.dedup.....94a592b2955c121f211fc9d610f3d3b4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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