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

Kylee H. Maclachlan, Even H. Rustad, Andriy Derkach, Binbin Zheng-Lin, Venkata Yellapantula, Benjamin Diamond, Malin Hultcrantz, Bachisio Ziccheddu, Eileen M. Boyle, Patrick Blaney, Niccolò Bolli, Yanming Zhang, Ahmet Dogan, Alexander M. Lesokhin, Gareth J. Morgan, Ola Landgren, Francesco Maura

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number5172
JournalNature Communications
Issue number1
Publication statusPublished - Dec 2021

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


Dive into the research topics of 'Copy number signatures predict chromothripsis and clinical outcomes in newly diagnosed multiple myeloma'. Together they form a unique fingerprint.

Cite this