Copy number signatures predict chromothripsis and clinical outcomes in newly diagnosed multiple myeloma
Year: 2021
Type: article
Study design: Observational Study
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.
Source: Nature Communications
Authors: 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
Institutions: Memorial Sloan Kettering Cancer Center, Oslo University Hospital, University of Miami, Sylvester Comprehensive Cancer Center, University of Turin, NYU Langone Health, NYU Langone’s Laura and Isaac Perlmutter Cancer Center, University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Weill Cornell Medicine
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,560
Funders: U.S. Department of Health and Human Services, Multiple Myeloma Research Foundation, American Society of Hematology, International Myeloma Foundation, Memorial Sloan-Kettering Cancer Center, Royal College of Pathologists of Australasia, Society of Memorial Sloan Kettering, Sylvester Comprehensive Cancer Center, University of Miami Health Systems, European Commission, Royal Australasian College of Physicians, Haematology Society of Australia and New Zealand, Snowdome Foundation, National Cancer Institute, Division of Cancer Epidemiology and Genetics, National Cancer Institute, H2020 European Research Council
Awards: spontaneous Evolution and Clonal heterOgeneity in MoNoclonal Gammopathies: from mechanisms of progression to clinical management, G2156476721, G2227505777, G2246262118, G289723095, G305175183, G4102770861, G434337789, G4708919113, G4737630392, Cancer Center Support Grant, The Sylvester Cancer Center Support Grant
OpenAlex ID: W3193484507