A case report of multiple primary prostate tumors with differential drug sensitivity

Scott Wilkinson, Stephanie A. Harmon, Nicholas T. Terrigino, Fatima Karzai, Peter A. Pinto, Ravi A. Madan, David J. VanderWeele, Ross Lake, Rayann Atway, John R. Bright, Nicole V. Carrabba, Shana Y. Trostel, Rosina T. Lis, Guinevere Chun, James L. Gulley, Maria J. Merino, Peter L. Choyke, Huihui Ye, William L. Dahut, Baris Turkbey and Adam G. Sowalsky ()
Additional contact information
Scott Wilkinson: Laboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute
Stephanie A. Harmon: Molecular Imaging Program, National Cancer Institute
Nicholas T. Terrigino: Laboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute
Fatima Karzai: Genitourinary Malignancies Branch, National Cancer Institute
Peter A. Pinto: Urologic Oncology Branch, National Cancer Institute
Ravi A. Madan: Genitourinary Malignancies Branch, National Cancer Institute
David J. VanderWeele: Laboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute
Ross Lake: Laboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute
Rayann Atway: Laboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute
John R. Bright: Laboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute
Nicole V. Carrabba: Laboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute
Shana Y. Trostel: Laboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute
Rosina T. Lis: Laboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute
Guinevere Chun: Genitourinary Malignancies Branch, National Cancer Institute
James L. Gulley: Genitourinary Malignancies Branch, National Cancer Institute
Maria J. Merino: Laboratory of Pathology, National Cancer Institute
Peter L. Choyke: Molecular Imaging Program, National Cancer Institute
Huihui Ye: Beth Israel Deaconess Medical Center
William L. Dahut: Genitourinary Malignancies Branch, National Cancer Institute
Baris Turkbey: Molecular Imaging Program, National Cancer Institute
Adam G. Sowalsky: Laboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute

Nature Communications, 2020, vol. 11, issue 1, 1-8

Abstract: Abstract Localized prostate cancers are genetically variable and frequently multifocal, comprising spatially distinct regions with multiple independently-evolving clones. To date there is no understanding of whether this variability can influence management decisions for patients with prostate tumors. Here, we present a single case from a clinical trial of neoadjuvant intense androgen deprivation therapy. A patient was diagnosed with a large semi-contiguous tumor by imaging, histologically composed of a large Gleason score 9 tumor with an adjacent Gleason score 7 nodule. DNA sequencing demonstrates these are two independent tumors, as only the Gleason 9 tumor harbors single-copy losses of PTEN and TP53. The PTEN/TP53-deficient tumor demonstrates treatment resistance, selecting for subclones with mutations to the remaining copies of PTEN and TP53, while the Gleason 7 PTEN-intact tumor is almost entirely ablated. These findings indicate that spatiogenetic variability is a major confounder for personalized treatment of patients with prostate cancer.

Date: 2020
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DOI: 10.1038/s41467-020-14657-7

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