title: Age-specific incidence data indicate four mutations are required for human testicular cancers.
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.
authors: Department of Biomedical Engineering, Center for Complex Biological Systems, University of California Irvine, Irvine, California, United States of America. jpbrody@uci.edu
authors: James P
authors: JP
authors: Brody
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009154:Mutation; D013736:Testicular Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D055815:Young Adult