Genomic and phenotypic heterogeneity in prostate cancer

Nat Rev Urol. 2021 Feb;18(2):79-92. doi: 10.1038/s41585-020-00400-w.

Michael C Haffner ¹ ² ³, Wilbert Zwart ⁴, Martine P Roudier ⁵, Lawrence D True ⁶, William G Nelson ⁷ ⁸ ⁹, Jonathan I Epstein ⁷ ⁸ ⁹, Angelo M De Marzo ⁷ ⁸ ⁹, Peter S Nelson ¹⁰, Srinivasan Yegnasubramanian ⁸

Affiliations

1 Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. mhaffner@fredhutch.org.
2 Department of Pathology, University of Washington, Seattle, WA, USA. mhaffner@fredhutch.org.
3 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. mhaffner@fredhutch.org.
4 Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, Netherlands.
5 Department of Urology, University of Washington, Seattle, WA, USA.
6 Department of Pathology, University of Washington, Seattle, WA, USA.
7 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
8 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
9 Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
10 Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

PMID: 33328650 DOI: 10.1038/s41585-020-00400-w

Abstract

From a clinical, morphological and molecular perspective, prostate Cancer is a heterogeneous disease. Primary prostate cancers are often multifocal, having topographically and morphologically distinct tumour foci. Sequencing studies have revealed that individual tumour foci can arise as clonally distinct lesions with no shared driver gene alterations. This finding demonstrates that multiple genomically and phenotypically distinct primary prostate cancers can be present in an individual patient. Lethal metastatic prostate Cancer seems to arise from a single clone in the primary tumour but can exhibit subclonal heterogeneity at the genomic, epigenetic and phenotypic levels. Collectively, this complex heterogeneous constellation of molecular alterations poses obstacles for the diagnosis and treatment of prostate Cancer. However, advances in our understanding of intra-tumoural heterogeneity and the development of novel technologies will allow us to navigate these challenges, refine approaches for translational research and ultimately improve patient care.

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