Gene Fusions

Chapter
Part of the Molecular Pathology Library book series (MPLB)

Abstract

Structural rearrangements have been recognized as hallmarks of cancer development and progression for a long time. Although initially thought to be almost exclusively a characteristic of hematological malignancies and mesenchymal neoplasia, the discovery that about 50% of prostate cancers, the second most common cancer in the USA, harbor ERG fusions revolutionized our view of their role in epithelial tumors. Since that discovery, several other fusions have been reported in other common solid tumors.

In prostate cancer, fusions typically follow the pattern of dysregulation of a member of the ETS family of transcription factors via the juxtaposition of an androgen-regulated 5′ partner. However, fusions involving RAF kinase family members have been reported, and more recently, new targeted therapies acting on the androgen receptor have shown that fusions may arise in the cancer tissue to contrast the therapeutic intervention, suggesting the need for different strategies of treatment.

In this chapter, the captivating history of the discovery of gene fusions, our current understanding of their biological and functional relevance, their implication on tumor evolution, and on clinical management of prostate cancer will be reviewed.

Keywords

Chimeric transcripts ETS family of transcription factors ETS rearrangements TMPRSS2-ERG RAF fusions Precision medicine 

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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory Medicine, Institute for Computational Biomedicine, Englander Institute for Precision MedicineWeill Cornell Medicine, New York Presbyterian HospitalNew YorkUSA

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