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PLoS One. 2011;6(10):e25978. doi: 10.1371/journal.pone.0025978. Epub 2011 Oct 6.

Age-specific incidence data indicate four mutations are required for human testicular cancers.

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  • 1Department of Biomedical Engineering, Center for Complex Biological Systems, University of California Irvine, Irvine, California, United States of America. jpbrody@uci.edu

Abstract

Normal human cells require a series of genetic alterations to undergo malignant transformation. Direct sequencing of human tumors has identified hundreds of mutations in tumors, but many of these are thought to be unnecessary and a result of, rather than a cause of, the tumor. The exact number of mutations to transform a normal human cell into a tumor cell is unknown. Here I show that male gonadal germ cell tumors, the most common form of testicular cancers, occur after four mutations. I infer this by constructing a mathematical model based upon the multi-hit hypothesis and comparing it to the age-specific incidence data. This result is consistent with the multi-hit hypothesis, and implies that these cancers are genetically or epigenetically predetermined at birth or an early age.

PMID:
21998737
[PubMed - indexed for MEDLINE]
PMCID:
PMC3188587
Free PMC Article
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