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Revealing the impact of recurrent and rare structural variants in multiple myeloma

Authors :
Philippe Moreau
Malin Hultcrantz
Venkata Yellapantula
Jonathan J Keats
Nicos Angelopoulos
Ahmet Dogan
Hervé Avet-Loiseau
Cody Ashby
Ola Landgren
Peter J. Campbell
Patrick Blaney
Yanming Zhang
Nikhil C. Munshi
Eileen M Boyle
Gareth J. Morgan
Gunes Gundem
Daniel Auclair
Niccolo Bolli
Francesco Maura
Even H Rustad
Elli Papaemmanuil
Benjamin Diamond
Daniel Leongamornlert
Dominik Glodzik
Kenneth C. Anderson
Kylee H Maclachlan
Publication Year :
2019
Publisher :
Cold Spring Harbor Laboratory, 2019.

Abstract

SummaryThe landscape of structural variants (SVs) in multiple myeloma remains poorly understood. Here, we performed comprehensive classification and analysis of SVs in multiple myeloma, interrogating a large cohort of 762 patients with whole genome and RNA sequencing. We identified 100 SV hotspots involving 31 new candidate driver genes, including drug targets BCMA (TNFRSF17) and SLAMF7. Complex SVs, including chromothripsis and templated insertions, were present in 61 % of patients and frequently resulted in the simultaneous acquisition of multiple drivers. After accounting for all recurrent events, 63 % of SVs remained unexplained. Intriguingly, these rare SVs were associated with up to 7-fold enrichment for outlier gene expression, indicating that many rare driver SVs remain unrecognized and are likely important in the biology of individual tumors.

Details

Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....988e768e28e8d884263e8ec25b0ddddf
Full Text :
https://doi.org/10.1101/2019.12.18.881086