What makes oncogenes mutually exclusive?

Cancer is driven by mutations in genes whose products participate in major signaling pathways that fuel cell proliferation and survival. It is easy to assume that the more of these so-called driver mutations a tumor accumulates, the faster it progresses. However, this does not appear to be the case:...

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Bibliographic Details
Published in:Small GTPases 2017-07, Vol.8 (3), p.187-192
Main Authors: Cisowski, Jaroslaw, Bergo, Martin O.
Format: Article
Language:English
Subjects:
Animals
Cell Death - genetics
Cellular Senescence - genetics
Gene Expression Regulation, Neoplastic
Humans
Mutation
mutual exclusivity
Neoplasms - genetics
Neoplasms - pathology
oncogene
Oncogenes - genetics
RAF
RAS
senescence
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Summary:Cancer is driven by mutations in genes whose products participate in major signaling pathways that fuel cell proliferation and survival. It is easy to assume that the more of these so-called driver mutations a tumor accumulates, the faster it progresses. However, this does not appear to be the case: Data from large-scale genome sequencing studies indicate that mutations in driver oncogenes often are mutually exclusive. The mechanisms underlying the mutual exclusivity of oncogenes are not completely understood, but recent reports suggest that the mechanisms may depend on the tumor type, and the nature of interacting oncogenes. Here we discuss our recent findings that the oncogenes KRAS G12D and BRAF V600E are mutually exclusive in lung cancer in mouse models because their coexpression leads to oncogene-induced senescence.
ISSN:2154-1248
2154-1256
DOI:10.1080/21541248.2016.1212689