A pan-cancer analysis of the frequency of DNA alterations across cell cycle activity levels.
Date
2020-08-06ICR Author
Author
Lundberg, A
Lindström, LS
Parker, JS
Löverli, E
Perou, CM
Bergh, J
Tobin, NP
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Aged
Cell Cycle
DNA
Female
Humans
Male
Middle Aged
Research team
Cancer Biomarkers
Language
eng
Date accepted
2020-06-10
License start date
2020-08-06
Citation
Oncogene, 2020, 39 (32), pp. 5430 - 5440
Publisher
SPRINGERNATURE