TY - JOUR
T1 - Chromosomal copy number heterogeneity predicts survival rates across cancers
AU - van Dijk, Erik
AU - van den Bosch, Tom
AU - Lenos, Kristiaan J.
AU - el Makrini, Khalid
AU - Nijman, Lisanne E.
AU - van Essen, Hendrik F. B.
AU - Lansu, Nico
AU - Boekhout, Michiel
AU - Hageman, Joris H.
AU - Fitzgerald, Rebecca C.
AU - Punt, Cornelis J. A.
AU - Tuynman, Jurriaan B.
AU - Snippert, Hugo J. G.
AU - Kops, Geert J. P. L.
AU - Medema, Jan Paul
AU - Ylstra, Bauke
AU - Vermeulen, Louis
AU - Miedema, Daniël M.
N1 - Funding Information: This work was supported by Amsterdam UMC and Oncode, by CRUK and MRC for the development and characterization of organoids, by a KWF and an intramural grant of the Pathology department of Amsterdam UMC to B.Y., by a talent development grant of the AG&M institute of Amsterdam UMC and a Young Investigator Grant of KWF to D.M.M.; L.V. is a New York Stem Cell Foundation—Robertson Investigator. We thank The Cancer Genome Atlas, the International Cancer Genome Consortium, the TRA-CERx consortium and J. Brenton for providing data. Publisher Copyright: © 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Survival rates of cancer patients vary widely within and between malignancies. While genetic aberrations are at the root of all cancers, individual genomic features cannot explain these distinct disease outcomes. In contrast, intra-tumour heterogeneity (ITH) has the potential to elucidate pan-cancer survival rates and the biology that drives cancer prognosis. Unfortunately, a comprehensive and effective framework to measure ITH across cancers is missing. Here, we introduce a scalable measure of chromosomal copy number heterogeneity (CNH) that predicts patient survival across cancers. We show that the level of ITH can be derived from a single-sample copy number profile. Using gene-expression data and live cell imaging we demonstrate that ongoing chromosomal instability underlies the observed heterogeneity. Analysing 11,534 primary cancer samples from 37 different malignancies, we find that copy number heterogeneity can be accurately deduced and predicts cancer survival across tissues of origin and stages of disease. Our results provide a unifying molecular explanation for the different survival rates observed between cancer types.
AB - Survival rates of cancer patients vary widely within and between malignancies. While genetic aberrations are at the root of all cancers, individual genomic features cannot explain these distinct disease outcomes. In contrast, intra-tumour heterogeneity (ITH) has the potential to elucidate pan-cancer survival rates and the biology that drives cancer prognosis. Unfortunately, a comprehensive and effective framework to measure ITH across cancers is missing. Here, we introduce a scalable measure of chromosomal copy number heterogeneity (CNH) that predicts patient survival across cancers. We show that the level of ITH can be derived from a single-sample copy number profile. Using gene-expression data and live cell imaging we demonstrate that ongoing chromosomal instability underlies the observed heterogeneity. Analysing 11,534 primary cancer samples from 37 different malignancies, we find that copy number heterogeneity can be accurately deduced and predicts cancer survival across tissues of origin and stages of disease. Our results provide a unifying molecular explanation for the different survival rates observed between cancer types.
UR - http://www.scopus.com/inward/record.url?scp=85106969717&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-021-23384-6
DO - https://doi.org/10.1038/s41467-021-23384-6
M3 - Article
C2 - 34045449
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3188
ER -