DNA replication stress mediates APOBEC3 family mutagenesis in breast cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-12

AUTHORS

Nnennaya Kanu, Maria Antonietta Cerone, Gerald Goh, Lykourgos-Panagiotis Zalmas, Jirina Bartkova, Michelle Dietzen, Nicholas McGranahan, Rebecca Rogers, Emily K. Law, Irina Gromova, Maik Kschischo, Michael I. Walton, Olivia W. Rossanese, Jiri Bartek, Reuben S. Harris, Subramanian Venkatesan, Charles Swanton

ABSTRACT

BACKGROUND: The APOBEC3 family of cytidine deaminases mutate the cancer genome in a range of cancer types. Although many studies have documented the downstream effects of APOBEC3 activity through next-generation sequencing, less is known about their upstream regulation. In this study, we sought to identify a molecular basis for APOBEC3 expression and activation. RESULTS: HER2 amplification and PTEN loss promote DNA replication stress and APOBEC3B activity in vitro and correlate with APOBEC3 mutagenesis in vivo. HER2-enriched breast carcinomas display evidence of elevated levels of replication stress-associated DNA damage in vivo. Chemical and cytotoxic induction of replication stress, through aphidicolin, gemcitabine, camptothecin or hydroxyurea exposure, activates transcription of APOBEC3B via an ATR/Chk1-dependent pathway in vitro. APOBEC3B activation can be attenuated through repression of oncogenic signalling, small molecule inhibition of receptor tyrosine kinase signalling and alleviation of replication stress through nucleoside supplementation. CONCLUSION: These data link oncogene, loss of tumour suppressor gene and drug-induced replication stress with APOBEC3B activity, providing new insights into how cytidine deaminase-induced mutagenesis might be activated in tumourigenesis and limited therapeutically. More... »

PAGES

185

References to SciGraph publications

  • 2015-11. SETD2 loss-of-function promotes renal cancer branched evolution through replication stress and impaired DNA repair in ONCOGENE
  • 2007-04. Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium in NATURE MEDICINE
  • 2013-02. APOBEC3B is an enzymatic source of mutation in breast cancer in NATURE
  • 2003-12. Mechanisms of apoptosis induction by nucleoside analogs in ONCOGENE
  • 2006-11. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints in NATURE
  • 2015-05. Replication stress and cancer in NATURE REVIEWS CANCER
  • 2013-09. The causes and consequences of genetic heterogeneity in cancer evolution in NATURE
  • 2016-07. RAD18, WRNIP1 and ATMIN promote ATM signalling in response to replication stress in ONCOGENE
  • 2005-04. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis in NATURE
  • 2016-12. deconstructSigs: delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution in GENOME BIOLOGY
  • 2013-02. Replication stress links structural and numerical cancer chromosomal instability in NATURE
  • 2013-09. An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers in NATURE GENETICS
  • 2013-09. Evidence for APOBEC3B mutagenesis in multiple human cancers in NATURE GENETICS
  • 2007-10. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis in ONCOGENE
  • 2014-01. Causes and consequences of replication stress in NATURE CELL BIOLOGY
  • 2013-08. Signatures of mutational processes in human cancer in NATURE
  • 2011-03. 53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress in NATURE CELL BIOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13059-016-1042-9

    DOI

    http://dx.doi.org/10.1186/s13059-016-1042-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1001918995

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27634334


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