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Prostate Cancer pp 57–66Cite as

Genetic, Environmental, and Nuclear Factors Governing Genomic Rearrangements

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1210))

Abstract

Studies employing whole genome and exome sequencing have revealed two remarkable features of prostate cancer (PCa)—the overall low mutation rates, and high rates of genomic rearrangements resulting in recurrent gene fusions. Genomic rearrangements involving the ETS transcription factor family genes are early driver events in PCa. These rearrangements typically involve the fusion of androgen-regulated transcriptionally active genes with the ETS genes (ERG, ETV1, ETV4 and ETV5), resulting in over-expression of fusion genes. The most prevalent ETS gene rearrangement, which is observed in >50% of PCa, involves the fusion of the androgen receptor (AR) target gene, TMPRSS2, with the ERG proto-oncogene, resulting in the formation of the TMPRSS2-ERG gene fusion. In this chapter, we consider the multitude of factors that influence the formation of recurrent genomic rearrangements in PCa. Understanding the mechanistic basis of gene fusion formation will shed light on unique features of PCa etiology and should impact several aspects of clinical disease management, ranging from prevention and early diagnosis to therapeutic targeting.

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Acknowledgements

We thank the members of the Mani laboratory for insights and comments; Peter Ly for discussions and manuscript edits. R.S.M. acknowledges funding support from the NIH Pathway to Independence (PI) Award (R00CA160640), the CPRIT Individual Investigator Research Award (RP190454), and the US Department of Defense Prostate Cancer Research Program (PCRP)—Impact Award (W81XWH-17-1-0675).

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Authors and Affiliations

  1. Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA

    Susmita G. Ramanand & Ram S. Mani

  2. Department of Urology, UT Southwestern Medical Center, Dallas, TX, USA

    Ram S. Mani

  3. Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA

    Ram S. Mani

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  1. Susmita G. Ramanand
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  2. Ram S. Mani
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Correspondence to Ram S. Mani .

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Editors and Affiliations

  1. Department of Laboratory Medicine and Pathology, Department of Urology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    Scott M. Dehm

  2. Departments of Urology, and Biochemistry & Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA

    Donald J. Tindall

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Ramanand, S.G., Mani, R.S. (2019). Genetic, Environmental, and Nuclear Factors Governing Genomic Rearrangements. In: Dehm, S., Tindall, D. (eds) Prostate Cancer. Advances in Experimental Medicine and Biology, vol 1210. Springer, Cham. https://doi.org/10.1007/978-3-030-32656-2_3

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