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Lundberg A, Lindström LS, Parker JS, Löverli E, Perou CM, Bergh J, Tobin NP
Oncogene 39 (32) 5430-5440 [2020-08-00; online 2020-06-24]
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.
PubMed 32581248
DOI 10.1038/s41388-020-1367-4
Crossref 10.1038/s41388-020-1367-4
mid: NIHMS1702965
pmc: PMC8159764
pii: 10.1038/s41388-020-1367-4