A pan-cancer analysis of the frequency of DNA alterations across cell cycle activity levels
- 24 June 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 39 (32), 5430-5440
- https://doi.org/10.1038/s41388-020-1367-4
Abstract
Pan-cancer genomic analyses based on the magnitude of pathway activity are currently lacking. Focusing on the cell cycle, we examined the DNA mutations and chromosome arm-level aneuploidy within tumours with low, intermediate and high cell-cycle activity in 9515 pan-cancer patients with 32 different tumour types. Boxplots showed that cell-cycle activity varied broadly across and within all cancers. TP53 and PIK3CA mutations were common in all cell cycle score (CCS) tertiles but with increasing frequency as cell-cycle activity levels increased (P < 0.001). Mutations in BRAF and gains in 16p were less frequent in CCS High tumours (P < 0.001). In Kaplan–Meier analysis, patients whose tumours were CCS Low had a longer Progression Free Interval (PFI) relative to Intermediate or High (P < 0.001) and this significance remained in multivariable analysis (CCS Intermediate: HR = 1.37; 95% CI 1.17–1.60, CCS High: 1.54; 1.29–1.84, CCS Low = Ref). These results demonstrate that whilst similar DNA alterations can be found at all cell-cycle activity levels, some notable exceptions exist. Moreover, independent prognostic information can be derived on a pan-cancer level from a simple measure of cell-cycle activity.Funding Information
- Iris, Stig och Gerry Castenbäcks Stiftelse for cancer research;
- Susan G. Komen (SAC-160074)
- Breast Cancer Research Foundation
- NCI Breast SPORE program
- Stiftelsen Konung Gustaf V:s Jubileumsfond
- Cancerfonden
- Vetenskapsrådet
- BRECT; Cancer Society in Stockholm Personalised Cancer Medicine (PCM); Swedish Breast Cancer Association;
This publication has 26 references indexed in Scilit:
- Genomic and Functional Approaches to Understanding Cancer AneuploidyCancer Cell, 2018
- Comprehensive Characterization of Cancer Driver Genes and MutationsCell, 2018
- Oncogenic Signaling Pathways in The Cancer Genome AtlasCell, 2018
- Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of OriginCell, 2014
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Cell Cycle Control and CancerScience, 1994
- Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2Nature, 1987
- Cyclin: A protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage divisionCell, 1983
- Genetic control of the cell division cycle in the fission yeast Schizosaccharomyces pombeMolecular Genetics and Genomics, 1976
- Genetic Control of the Cell Division Cycle in YeastScience, 1974