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Title: Understanding the origins of human cancer

Abstract

All cancers originate from a single cell that starts to behave abnormally, to divide uncontrollably, and, eventually, to invade adjacent tissues (1). The aberrant behavior of this single cell is due to somatic mutations—changes in the genomic DNA produced by the activity of different mutational processes (1). These various mutational processes include exposure to exogenous or endogenous mutagens, abnormal DNA editing, the incomplete fidelity of DNA polymerases, and failure of DNA repair mechanisms (2). Early studies that sequenced TP53, the most commonly mutated gene in human cancer, provided evidence that mutational processes leave distinct imprints of somatic mutations on the genome of a cancer cell (3). For example, C:G>A:T transversions predominate in smoking-associated lung cancer, whereas C:G>T:A transitions occurring mainly at dipyrimidines and CC:GG>TT:AA double-nucleotide substitutions are common in ultraviolet light–associated skin cancers. Moreover, these patterns of mutations matched the ones induced experimentally by tobacco mutagens and ultraviolet light, respectively, the major, known, exogenous carcinogenic influences in these cancer types, and demonstrated that examining patterns of mutations in cancer genomes can yield information about the mutational processes that cause human cancer (4).

Authors:
 [1]
+ Show Author Affiliations
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Publication Date:
Research Org.:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1240626
Report Number(s):
LA-UR-15-28485
Journal ID: ISSN 0036-8075
Grant/Contract Number:  
AC52-06NA25396
Resource Type:
Accepted Manuscript
Journal Name:
Science
Additional Journal Information:
Journal Volume: 350; Journal Issue: 6265; Journal ID: ISSN 0036-8075
Publisher:
AAAS
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Alexandrov, L. B. Understanding the origins of human cancer. United States: N. p., 2015. Web. doi:10.1126/science.aad7363.
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Alexandrov, L. B. Understanding the origins of human cancer. United States. https://doi.org/10.1126/science.aad7363
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Alexandrov, L. B. Fri . "Understanding the origins of human cancer". United States. https://doi.org/10.1126/science.aad7363. https://www.osti.gov/servlets/purl/1240626.
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@article{osti_1240626,
title = {Understanding the origins of human cancer},
author = {Alexandrov, L. B.},
abstractNote = {All cancers originate from a single cell that starts to behave abnormally, to divide uncontrollably, and, eventually, to invade adjacent tissues (1). The aberrant behavior of this single cell is due to somatic mutations—changes in the genomic DNA produced by the activity of different mutational processes (1). These various mutational processes include exposure to exogenous or endogenous mutagens, abnormal DNA editing, the incomplete fidelity of DNA polymerases, and failure of DNA repair mechanisms (2). Early studies that sequenced TP53, the most commonly mutated gene in human cancer, provided evidence that mutational processes leave distinct imprints of somatic mutations on the genome of a cancer cell (3). For example, C:G>A:T transversions predominate in smoking-associated lung cancer, whereas C:G>T:A transitions occurring mainly at dipyrimidines and CC:GG>TT:AA double-nucleotide substitutions are common in ultraviolet light–associated skin cancers. Moreover, these patterns of mutations matched the ones induced experimentally by tobacco mutagens and ultraviolet light, respectively, the major, known, exogenous carcinogenic influences in these cancer types, and demonstrated that examining patterns of mutations in cancer genomes can yield information about the mutational processes that cause human cancer (4).},
doi = {10.1126/science.aad7363},
journal = {Science},
number = 6265,
volume = 350,
place = {United States},
year = {Fri Dec 04 00:00:00 EST 2015},
month = {Fri Dec 04 00:00:00 EST 2015}
}
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https://doi.org/10.1126/science.aad7363
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    Works referencing / citing this record:

    Mutational signature analysis identifies MUTYH deficiency in colorectal cancers and adrenocortical carcinomas: Mutational signature associated with MUTYH deficiency in cancers
    journal, March 2017

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    Nonnegative tensor decomposition with custom clustering for microphase separation of block copolymers
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    • Statistical Analysis and Data Mining: The ASA Data Science Journal, Vol. 12, Issue 4
    • DOI: 10.1002/sam.11407

    Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours
    journal, February 2018

    Understanding mutagenesis through delineation of mutational signatures in human cancer
    journal, May 2016

    Revertant mosaicism repairs skin lesions in a patient with keratitis-ichthyosis-deafness syndrome by second-site mutations in connexin 26
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    High Risk of Hepatocellular Carcinoma Development in Fibrotic Liver: Role of the Hippo-YAP/TAZ Signaling Pathway
    journal, January 2019

    • Moon, Hyuk; Cho, Kyungjoo; Shin, Sunyeong
    • International Journal of Molecular Sciences, Vol. 20, Issue 3
    • DOI: 10.3390/ijms20030581

    Mutational signatures associated with tobacco smoking in human cancer
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    The repertoire of mutational signatures in human cancer
    text, January 2020

    • Alexandrov, Ludmil B.; Kim, Jaegil; Haradhvala, Nicholas J.
    • Apollo - University of Cambridge Repository
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    The repertoire of mutational signatures in human cancer
    journal, February 2020

    High Risk of Hepatocellular Carcinoma Development in Fibrotic Liver: Role of the Hippo-YAP/TAZ Signaling Pathway
    journal, January 2019

    • Moon, Hyuk; Cho, Kyungjoo; Shin, Sunyeong
    • International Journal of Molecular Sciences, Vol. 20, Issue 3
    • DOI: 10.3390/ijms20030581
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