Synapse - Revealing the impact of structural variants in multiple myeloma

Revealing the impact of structural variants in multiple myeloma Journal Article

Authors:	Rustad, E. H.; Yellapantula, V. D.; Glodzik, D.; Maclachlan, K. H.; Diamond, B.; Boyle, E. M.; Ashby, C.; Blaney, P.; Gundem, G.; Hultcrantz, M.; Leongamornlert, D.; Angelopoulos, N.; Agnelli, L.; Auclair, D.; Zhang, Y.; Dogan, A.; Bolli, N.; Papaemmanuil, E.; Anderson, K. C.; Moreau, P.; Avet-Loiseau, H.; Munshi, N. C.; Keats, J. J.; Campbell, P. J.; Morgan, G. J.; Landgren, O.; Maura, F.
Article Title:	Revealing the impact of structural variants in multiple myeloma
Abstract:	The landscape of structural variants (SV) in multiple myeloma remains poorly understood. Here, we performed comprehensive analysis of SVs in a large cohort of 752 patients with multiple myeloma 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), SLAM7, 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. ©2020 American Association for Cancer Research.
Keywords:	genetics; multiple myeloma; oncogenes; oncogene; genomics; procedures; chromothripsis; humans; human; whole genome sequencing
Journal Title:	Blood Cancer Discovery
Volume:	1
Issue:	3
ISSN:	2643-3230
Publisher:	American Association for Cancer Research
Date Published:	2020-11-01
Start Page:	259
End Page:	273
Language:	English
DOI:	10.1158/2643-3230.Bcd-20-0132
PUBMED:	33392515
PROVIDER:	scopus
PMCID:	PMC7774871
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85097208547&doi=10.1158%2f2643-3230.BCD-20-0132&partnerID=40&md5=3c84ff28b5076a94c79ebd8b7b686372
Notes:	Article -- Source: Scopus