| Literature DB >> 33392515 |
Ola Landgren1, Francesco Maura2, Even H Rustad1, Venkata D Yellapantula1, Dominik Glodzik3, Kylee H Maclachlan1, Benjamin Diamond1, Eileen M Boyle4, Cody Ashby5, Patrick Blaney4, Gunes Gundem3, Malin Hultcrantz1, Daniel Leongamornlert6, Nicos Angelopoulos6,7, Luca Agnelli8, Daniel Auclair9, Yanming Zhang10, Ahmet Dogan11, Niccolò Bolli12,13, Elli Papaemmanuil3, Kenneth C Anderson14, Philippe Moreau15, Hervé Avet-Loiseau16, Nikhil C Munshi14,17, Jonathan J Keats18, Peter J Campbell6, Gareth J Morgan4.
Abstract
The landscape of structural variants (SVs) in multiple myeloma remains poorly understood. Here, we performed comprehensive analysis of SVs in a large cohort of 752 multiple myeloma patients by low coverage long-insert whole genome sequencing. We identified 68 SV hotspots involving 17 new candidate driver genes, including the therapeutic targets BCMA (TNFRSF17), SLAMF and MCL1. Catastrophic complex rearrangements termed chromothripsis were present in 24% of patients and independently associated with poor clinical outcomes. Templated insertions were the second most frequent complex event (19%), mostly involved in super-enhancer hijacking and activation of oncogenes such as CCND1 and MYC. Importantly, in 31% of patients two or more seemingly independent putative driver events were caused by a single structural event, demonstrating that the complex genomic landscape of multiple myeloma can be acquired through few key events during tumor evolutionary history. Overall, this study reveals the critical role of SVs in multiple myeloma pathogenesis.Entities:
Keywords: chromoplexy; chromothripsis; hotspots; multiple myeloma; structural variants; templated insertion
Mesh：
Year: 2020 PMID： 33392515 PMCID： PMC7774871 DOI： 10.1158/2643-3230.BCD-20-0132
Source DB: PubMed Journal: Blood Cancer Discov ISSN： 2643-3230