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Age-Specific Incidence Data Indicate Four Mutations Are Required for Human Testicular Cancers
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 mu...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188587/ https://www.ncbi.nlm.nih.gov/pubmed/21998737 http://dx.doi.org/10.1371/journal.pone.0025978 |
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author | Brody, James P. |
author_facet | Brody, James P. |
author_sort | Brody, James P. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3188587 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31885872011-10-13 Age-Specific Incidence Data Indicate Four Mutations Are Required for Human Testicular Cancers Brody, James P. PLoS One Research Article 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. Public Library of Science 2011-10-06 /pmc/articles/PMC3188587/ /pubmed/21998737 http://dx.doi.org/10.1371/journal.pone.0025978 Text en James P. Brody. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Brody, James P. Age-Specific Incidence Data Indicate Four Mutations Are Required for Human Testicular Cancers |
title | Age-Specific Incidence Data Indicate Four Mutations Are Required for Human Testicular Cancers |
title_full | Age-Specific Incidence Data Indicate Four Mutations Are Required for Human Testicular Cancers |
title_fullStr | Age-Specific Incidence Data Indicate Four Mutations Are Required for Human Testicular Cancers |
title_full_unstemmed | Age-Specific Incidence Data Indicate Four Mutations Are Required for Human Testicular Cancers |
title_short | Age-Specific Incidence Data Indicate Four Mutations Are Required for Human Testicular Cancers |
title_sort | age-specific incidence data indicate four mutations are required for human testicular cancers |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188587/ https://www.ncbi.nlm.nih.gov/pubmed/21998737 http://dx.doi.org/10.1371/journal.pone.0025978 |
work_keys_str_mv | AT brodyjamesp agespecificincidencedataindicatefourmutationsarerequiredforhumantesticularcancers |