Passenger Hotspot Mutations in Cancer.

Cancer Cell
Authors
Abstract

Current statistical models for assessing hotspot significance do not properly account for variation in site-specific mutability, thereby yielding many false-positives. We thus (i) detail a Log-normal-Poisson (LNP) background model that accounts for this variability in a manner consistent with models of mutagenesis; (ii) use it to show that passenger hotspots arise from all common mutational processes; and (iii) apply it to a ∼10,000-patient cohort to nominate driver hotspots with far fewer false-positives compared with conventional methods. Overall, we show that many cancer hotspot mutations recurring at the same genomic site across multiple tumors are actually passenger events, recurring at inherently mutable genomic sites under no positive selection.

Year of Publication
2019
Journal
Cancer Cell
Volume
36
Issue
3
Pages
288-301.e14
Date Published
2019 Sep 16
ISSN
1878-3686
DOI
10.1016/j.ccell.2019.08.002
PubMed ID
31526759
Links