HER2 is not a cancer subtype but rather a pan-cancer event and is highly enriched in AR-driven breast tumors.

Background: Approximately one in five breast cancers are driven by amplification and overexpression of the human epidermal growth factor receptor 2 (HER2) receptor kinase, and HER2-enriched (HER2E) is one of four major transcriptional subtypes of breast cancer. We set out to understand the genomics...

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Publicado en:Breast Cancer Research Vol. 20; pp. 1 - 17
Autores principales: Daemen, Anneleen, Manning, Gerard
Formato: Journal Article
Publicado: BioMed Central 1/30/2018
Acceso en línea:Ver este registro en EBSCOhost
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        14655411
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      dt: 1/30/2018
      vid: 20
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      pub: BioMed Central
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        10.1186/s13058-018-0933-y
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        atl: HER2 is not a cancer subtype but rather a pan-cancer event and is highly enriched in AR-driven breast tumors.
      aug:
        au:
          Daemen, Anneleen
          Manning, Gerard
        affil: Bioinformatics & Computational Biology, Genentech, Inc, 1 DNA Way, MS444a, 94080, South San Francisco, CA, USA
      sug:
        subj:
          Proteins
          Receptors, Cell Surface
          Breast Neoplasms
          Neoplastic Processes
          Receptors, Cell Surface Antagonists and Inhibitors
          Proteins Antagonists and Inhibitors
          Genes
          Breast Neoplasms Drug Therapy
          Breast Neoplasms Classification
          Female
          Breast Neoplasms Pathology
          Female
      ab: Background: Approximately one in five breast cancers are driven by amplification and overexpression of the human epidermal growth factor receptor 2 (HER2) receptor kinase, and HER2-enriched (HER2E) is one of four major transcriptional subtypes of breast cancer. We set out to understand the genomics of HER2 amplification independent of subtype, and the underlying drivers and biology of HER2E tumors.Methods: We investigated published genomic data from 3155 breast tumors and 5391 non-breast tumors.Results: HER2 amplification is a distinct driver event seen in all breast cancer subtypes, rather than a subtype marker, with major characteristics restricted to amplification and overexpression of HER2 and neighboring genes. The HER2E subtype has a distinctive transcriptional landscape independent of HER2A that reflects androgen receptor signaling as replacement for estrogen receptor (ER)-driven tumorigenesis. HER2 amplification is also an event in 1.8% of non-breast tumors.Conclusions: These discoveries reveal therapeutic opportunities for combining anti-HER2 therapy with anti-androgen agents in breast cancer, and highlight the potential for broader therapeutic use of HER2 inhibitors.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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