Copy number signatures predict chromothripsis and clinical outcomes in newly diagnosed multiple myeloma Journal Article

   


Authors: Maclachlan, K. H.; Rustad, E. H.; Derkach, A.; Zheng-Lin, B.; Yellapantula, V.; Diamond, B.; Hultcrantz, M.; Ziccheddu, B.; Boyle, E. M.; Blaney, P.; Bolli, N.; Zhang, Y.; Dogan, A.; Lesokhin, A. M.; Morgan, G. J.; Landgren, O.; Maura, F.
Article Title: Copy number signatures predict chromothripsis and clinical outcomes in newly diagnosed multiple myeloma
Abstract: Chromothripsis is detectable in 20–30% of newly diagnosed multiple myeloma (NDMM) patients and is emerging as a new independent adverse prognostic factor. In this study we interrogate 752 NDMM patients using whole genome sequencing (WGS) to investigate the relationship of copy number (CN) signatures to chromothripsis and show they are highly associated. CN signatures are highly predictive of the presence of chromothripsis (AUC = 0.90) and can be used identify its adverse prognostic impact. The ability of CN signatures to predict the presence of chromothripsis is confirmed in a validation series of WGS comprised of 235 hematological cancers (AUC = 0.97) and an independent series of 34 NDMM (AUC = 0.87). We show that CN signatures can also be derived from whole exome data (WES) and using 677 cases from the same series of NDMM, we are able to predict both the presence of chromothripsis (AUC = 0.82) and its adverse prognostic impact. CN signatures constitute a flexible tool to identify the presence of chromothripsis and is applicable to WES and WGS data. © 2021, The Author(s).
Keywords: chromosome; protein; blood; genome; model validation
Journal Title: Nature Communications
Volume: 12
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2021-08-27
Start Page: 5172
Language: English
DOI: 10.1038/s41467-021-25469-8
PUBMED: 34453055
PROVIDER: scopus
PMCID: PMC8397708
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85113739214&doi=10.1038%2fs41467-021-25469-8&partnerID=40&md5=269a4ba294e601ddaecb08682ef1803a
Notes: Article -- Export Date: 1 October 2021 -- Source: Scopus
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MSK Authors
  1. Ahmet Dogan
    454 Dogan
  2. Malin Lisa Hultcrantz
    260 Hultcrantz
  3. Yanming Zhang
    199 Zhang
  4. Venkata D Yellapantula
    51 Yellapantula
  5. Even Holth Rustad
    43 Rustad
  6. Benjamin Diamond
    33 Diamond
  7. Kylee Maclachlan
    143 Maclachlan
  8. Andriy Derkach
    148 Derkach
  9. Binbin Zheng
    11 Zheng
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