DNA replication stress: a source of APOBEC3B expression in breast cancer.

David W Cescon,Benjamin Haibe-Kains

doi:10.1186/s13059-016-1069-y

Abstract

APOBEC cytidine deaminases have been implicated as major contributors to the mutation burden in many cancers on the basis of their mutational signature. A new experimental study sheds light on the inciting factors, linking APOBEC3B expression to oncogene- and drug-induced replication stress.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-1069-y) contains supplementary material, which is available to authorized users.

Highlights

APOBEC cytidine deaminases have been implicated as major contributors to the mutation burden in many cancers on the basis of their mutational signature
The biology is complicated by the existence of a common human germline deletion polymorphism in APOBEC3B, which eliminates the entire coding region of this gene but is paradoxically associated with an increased risk of breast cancer [5] and an increased burden of APOBEC-pattern mutations [6, 7]
Connecting replication stress and APOBEC3B through ATR Kanu and colleagues focused on the association between replication stress and APOBEC3B activity in breast cancer cell lines, starting from the observation that the HER2-enriched subtype of breast cancers exhibits the greatest burden of APOBEC mutations [8] and the premise that oncogene-induced replication stress exposes single

Summary

Introduction

APOBEC cytidine deaminases have been implicated as major contributors to the mutation burden in many cancers on the basis of their mutational signature. * Correspondence: dave.cescon@uhn.ca; bhaibeka@uhnresearch.ca 1Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada Full list of author information is available at the end of the article caused by one or more APOBECs. First identified in breast cancer datasets [3, 4], the mutagenic potential of the APOBEC family of enzymes had been recognized in preclinical systems, but the inferred mutational burden across a high proportion of tumor types represented a surprising discovery.

Results

Conclusion