TY - JOUR
T1 - APOBEC Enzymes
T2 - Mutagenic Fuel for Cancer Evolution and Heterogeneity
AU - Swanton, Charles
AU - McGranahan, Nicholas
AU - Starrett, Gabriel J.
AU - Harris, Reuben S.
N1 - Publisher Copyright:
©2015 American Association for Cancer Research.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - UNLABELLED: Deep sequencing technologies are revealing the complexities of cancer evolution, casting light on mutational processes fueling tumor adaptation, immune escape, and treatment resistance. Understanding mechanisms driving cancer diversity is a critical step toward developing strategies to attenuate tumor evolution and adaptation. One emerging mechanism fueling tumor diversity and subclonal evolution is genomic DNA cytosine deamination catalyzed by APOBEC3B and at least one other APOBEC family member. Deregulation of APOBEC3 enzymes causes a general mutator phenotype that manifests as diverse and heterogeneous tumor subclones. Here, we summarize knowledge of the APOBEC DNA deaminase family in cancer, and their role as driving forces for intratumor heterogeneity and a therapeutic target to limit tumor adaptation.SIGNIFICANCE: APOBEC mutational signatures may be enriched in tumor subclones, suggesting APOBEC cytosine deaminases fuel subclonal expansions and intratumor heterogeneity. APOBEC family members might represent a new class of drug target aimed at limiting tumor evolution, adaptation, and drug resistance.
AB - UNLABELLED: Deep sequencing technologies are revealing the complexities of cancer evolution, casting light on mutational processes fueling tumor adaptation, immune escape, and treatment resistance. Understanding mechanisms driving cancer diversity is a critical step toward developing strategies to attenuate tumor evolution and adaptation. One emerging mechanism fueling tumor diversity and subclonal evolution is genomic DNA cytosine deamination catalyzed by APOBEC3B and at least one other APOBEC family member. Deregulation of APOBEC3 enzymes causes a general mutator phenotype that manifests as diverse and heterogeneous tumor subclones. Here, we summarize knowledge of the APOBEC DNA deaminase family in cancer, and their role as driving forces for intratumor heterogeneity and a therapeutic target to limit tumor adaptation.SIGNIFICANCE: APOBEC mutational signatures may be enriched in tumor subclones, suggesting APOBEC cytosine deaminases fuel subclonal expansions and intratumor heterogeneity. APOBEC family members might represent a new class of drug target aimed at limiting tumor evolution, adaptation, and drug resistance.
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U2 - 10.1158/2159-8290.CD-15-0344
DO - 10.1158/2159-8290.CD-15-0344
M3 - Review article
C2 - 26091828
AN - SCOPUS:85018197468
SN - 2159-8274
VL - 5
SP - 704
EP - 712
JO - Cancer discovery
JF - Cancer discovery
IS - 7
ER -