English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  HER2 is overexpressed and amplified in approximately 15% of invasive breast cancers, and is the molecular target and predictive marker of response to anti-HER2 agents. In a subset of these cases, heterogeneous distribution of  HER2  gene amplification can be found, which creates clinically challenging scenarios. Currently, breast cancers with  HER2  amplification/overexpression in just over 10% of cancer cells are considered HER2-positive for clinical purposes; however, it is unclear as to whether the HER2-negative components of such tumors would be driven by distinct genetic alterations. Here we sought to characterize the pathologic and genetic features of the HER2-positive and HER2-negative components of breast cancers with heterogeneous  HER2  gene amplification and to define the repertoire of potential driver genetic alterations in the HER2-negative components of these cases.    Results  We separately analyzed the HER2-negative and HER2-positive components of 12 HER2 heterogeneous breast cancers using gene copy number profiling and massively parallel sequencing, and identified potential driver genetic alterations restricted to the HER2-negative cells in each case.  In vitro  experiments provided functional evidence to suggest that  BRF2  and  DSN1  overexpression/amplification, and the  HER2  I767M mutation may be alterations that compensate for the lack of  HER2  amplification in the HER2-negative components of HER2 heterogeneous breast cancers.    Conclusions  Our results indicate that even driver genetic alterations, such as  HER2  gene amplification, can be heterogeneously distributed within a cancer, and that the HER2-negative components are likely driven by genetic alterations not present in the HER2-positive components, including  BRF2  and  DSN1  amplification and  HER2  somatic mutations.    Electronic supplementary material  The online version of this article (doi:10.1186/s13059-015-0657-6) contains supplementary material, which is available to authorized users.

Intra-tumor genetic heterogeneity and alternative driver genetic alterations in breast cancers with heterogeneous HER2 gene amplification