Chromosomal copy number heterogeneity predicts survival rates across cancers

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 prognosis1,2. Unfortunately, a comprehensive and effective framework to measure ITH across cancers is missing3. Here, we introduce a scalable measure of chromosomal copy number heterogeneity 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 we demonstrate that ongoing chromosomal instability underlies the observed heterogeneity. Analysing 11,534 primary cancer samples from 35 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.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

2 Datasets 2 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001006438	Contains data for all cells sequenced for this study. Data is organized as one bam-file per sample. Individual cells can be identified through the CB tag in the bam-files.	NextSeq 500	7
EGAD00010002002	4 oesophageal cancer derived organoid lines and 2 ovarian cancer derived organoid lines	GSA-MD V3	6

Publications	Citations
Chromosomal copy number heterogeneity predicts survival rates across cancers. van Dijk E, van den Bosch T, Lenos KJ, El Makrini K, Nijman LE, van Essen HFB, Lansu N, Boekhout M, Hageman JH, Fitzgerald RC, Punt CJA, Tuynman JB, Snippert HJG, Kops GJPL, Medema JP, Ylstra B, Vermeulen L, Miedema DM. Nat Commun 12: 2021 3188	35
Molecular characterization of colorectal cancer related peritoneal metastatic disease. Lenos KJ, Bach S, Ferreira Moreno L, Ten Hoorn S, Sluiter NR, Bootsma S, Vieira Braga FA, Nijman LE, van den Bosch T, Miedema DM, van Dijk E, Ylstra B, Kulicke R, Davis FP, Stransky N, Smolen GA, Coebergh van den Braak RRJ, IJzermans JNM, Martens JWM, Hallam S, Beggs AD, Kops GJPL, Lansu N, Bastiaenen VP, Klaver CEL, Lecca MC, El Makrini K, Elbers CC, Dings MPG, van Noesel CJM, Kranenburg O, Medema JP, Koster J, Koens L, Punt CJA, Tanis PJ, de Hingh IH, Bijlsma MF, Tuynman JB, Vermeulen L. Nat Commun 13: 2022 4443	38

Publications

Citations

Chromosomal copy number heterogeneity predicts survival rates across cancers.
van Dijk E, van den Bosch T, Lenos KJ, El Makrini K, Nijman LE, van Essen HFB, Lansu N, Boekhout M, Hageman JH, Fitzgerald RC, Punt CJA, Tuynman JB, Snippert HJG, Kops GJPL, Medema JP, Ylstra B, Vermeulen L, Miedema DM. Nat Commun 12: 2021 3188

Molecular characterization of colorectal cancer related peritoneal metastatic disease.
Lenos KJ, Bach S, Ferreira Moreno L, Ten Hoorn S, Sluiter NR, Bootsma S, Vieira Braga FA, Nijman LE, van den Bosch T, Miedema DM, van Dijk E, Ylstra B, Kulicke R, Davis FP, Stransky N, Smolen GA, Coebergh van den Braak RRJ, IJzermans JNM, Martens JWM, Hallam S, Beggs AD, Kops GJPL, Lansu N, Bastiaenen VP, Klaver CEL, Lecca MC, El Makrini K, Elbers CC, Dings MPG, van Noesel CJM, Kranenburg O, Medema JP, Koster J, Koens L, Punt CJA, Tanis PJ, de Hingh IH, Bijlsma MF, Tuynman JB, Vermeulen L. Nat Commun 13: 2022 4443