title: Limitations of the Driver/Passenger Model in Cancer Prevention.
abstract: Mutations detected in cancers are often divided into "drivers" and "passengers." We suggest that this classification is potentially misleading for purposes of early detection and prevention. Specifically, some mutations are frequent in tumors and thus appear to be drivers, but are poor predictors of cancer; other mutations are individually rare and thus appear to be passengers, but may collectively explain a large proportion of risk. The assumptions bundled into the terms "driver" and "passenger" can lead to misunderstandings of neoplastic progression, with unintended consequences including overdiagnosis, overtreatment, and failure to identify the true sources of risk. We argue that samples from healthy, benign, or neoplastic tissues are critical for evaluating the risk of future cancer posed by mutations in a given gene. Cancer Prev Res; 9(5); 335-8. ©2016 AACR.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington. mkkuhner@uw.edu.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Kuhner
authors.affiliation: Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Rumen
authors.initials: R
authors.lastname: Kostadinov
authors.affiliation: Divisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Reid
mesh_terms: D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000517:prevention & control*