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The complexity of prostate cancer: genomic alterations and heterogeneity

Abstract

Although prostate cancer is the most common malignancy to affect men in the Western world, the molecular mechanisms underlying its development and progression remain poorly understood. Like all cancers, prostate cancer is a genetic disease that is characterized by multiple genomic alterations, including point mutations, microsatellite variations, and chromosomal alterations such as translocations, insertions, duplications, and deletions. In prostate cancer, but not other carcinomas, these chromosome alterations result in a high frequency of gene fusion events. The development and application of novel high-resolution technologies has significantly accelerated the detection of genomic alterations, revealing the complex nature and heterogeneity of the disease. The clinical heterogeneity of prostate cancer can be partly explained by this underlying genetic heterogeneity, which has been observed between patients from different geographical and ethnic populations, different individuals within these populations, different tumour foci within the same patient, and different cells within the same tumour focus. The highly heterogeneous nature of prostate cancer provides a real challenge for clinical disease management and a detailed understanding of the genetic alterations in all cells, including small subpopulations, would be highly advantageous.

Key Points

  • Prostate cancer is the most common malignancy reported in Western men; however, despite extensive investigation, the molecular mechanisms underlying its development and progression are still poorly understood

  • Like most cancers, prostate cancer is characterized by multiple genomic alterations, including point mutations, microsatellite sequence changes, and chromosomal rearrangements (such as translocations, insertions, duplications, and deletions)

  • Prostate cancer is associated with high levels of interpatient heterogeneity (including geographical and ethnic heterogeneity) and intrapatient heterogeneity (for example, interfocal and intrafocal heterogeneity)

  • Given its heterogeneity, clinical management of prostate cancer is challenging and requires a detailed understanding of the genetic alterations that occur in all cells, including small subpopulations

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Figure 1: Intrafocal heterogeneity at the PTEN locus.

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L. Boyd and Y.-J. Lu researched, wrote, discussed, and edited the article. X. Mao contributed towards researching the primary literature.

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Boyd, L., Mao, X. & Lu, YJ. The complexity of prostate cancer: genomic alterations and heterogeneity. Nat Rev Urol 9, 652–664 (2012). https://doi.org/10.1038/nrurol.2012.185

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