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

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.

SUBMITTER: Wilkinson S

PROVIDER: S-EPMC7018822 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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

Wilkinson Scott S Harmon Stephanie A SA Terrigino Nicholas T NT Karzai Fatima F Pinto Peter A PA Madan Ravi A RA VanderWeele David J DJ Lake Ross R Atway Rayann R Bright John R JR Carrabba Nicole V NV Trostel Shana Y SY Lis Rosina T RT Chun Guinevere G Gulley James L JL Merino Maria J MJ Choyke Peter L PL Ye Huihui H Dahut William L WL Turkbey Baris B Sowalsky Adam G AG

Nature communications 20200213 1

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 ...[more]

PMID: 32054861

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

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

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