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; Adam G. Sowalsky

doi:10.1038/s41467-020-14657-7

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 TurkbeyAdam G. Sowalsky^*

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

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.

Original language	English (US)
Article number	837
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-14657-7
State	Published - Dec 1 2020

Funding

The authors gratefully acknowledge the patient and the family of the patient who participated in this study. DNA sequencing was performed at the Center for Cancer Research (CCR) Genomics Core, the CCR Illumina Sequencing Facility, and the CCR Genomics Technology Laboratory. The authors acknowledge technical assistance from Steven Shema and Madeline Wong. Portions of this work utilized the computational resources of the NIH HPC Biowulf cluster. This work was supported by the Prostate Cancer Foundation (Young Investigator Awards to S.W., S.H., F.K., D.J.V., R.A.M., H.Y., and A.G.S.), the Department of Defense Prostate Cancer Research Program (W81XWH-19-1-0712 to S.W., W81XWH-16-1-0433 to A.G.S.), the National Cancer Institute (HHSN261200800001E) and the Intramural Research Program of the NIH, National Cancer Institute.

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

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10.1038/s41467-020-14657-7

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Wilkinson, S., Harmon, S. A., Terrigino, N. T., Karzai, F., Pinto, P. A., Madan, R. A., VanderWeele, D. J., Lake, R., Atway, R., Bright, J. R., Carrabba, N. V., Trostel, S. Y., Lis, R. T., Chun, G., Gulley, J. L., Merino, M. J., Choyke, P. L., Ye, H., Dahut, W. L., ... Sowalsky, A. G. (2020). A case report of multiple primary prostate tumors with differential drug sensitivity. Nature communications, 11(1), Article 837. https://doi.org/10.1038/s41467-020-14657-7

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title = "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.",

author = "Scott Wilkinson and Harmon, \{Stephanie A.\} and Terrigino, \{Nicholas T.\} and Fatima Karzai and Pinto, \{Peter A.\} and Madan, \{Ravi A.\} and VanderWeele, \{David J.\} and Ross Lake and Rayann Atway and Bright, \{John R.\} and Carrabba, \{Nicole V.\} and Trostel, \{Shana Y.\} and Lis, \{Rosina T.\} and Guinevere Chun and Gulley, \{James L.\} and Merino, \{Maria J.\} and Choyke, \{Peter L.\} and Huihui Ye and Dahut, \{William L.\} and Baris Turkbey and Sowalsky, \{Adam G.\}",

note = "Publisher Copyright: {\textcopyright} 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41467-020-14657-7",

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Wilkinson, S, Harmon, SA, Terrigino, NT, Karzai, F, Pinto, PA, Madan, RA, VanderWeele, DJ, Lake, R, Atway, R, Bright, JR, Carrabba, NV, Trostel, SY, Lis, RT, Chun, G, Gulley, JL, Merino, MJ, Choyke, PL, Ye, H, Dahut, WL, Turkbey, B & Sowalsky, AG 2020, 'A case report of multiple primary prostate tumors with differential drug sensitivity', Nature communications, vol. 11, no. 1, 837. https://doi.org/10.1038/s41467-020-14657-7

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AU - Harmon, Stephanie A.

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AU - Karzai, Fatima

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AU - Madan, Ravi A.

AU - VanderWeele, David J.

AU - Lake, Ross

AU - Atway, Rayann

AU - Bright, John R.

AU - Carrabba, Nicole V.

AU - Trostel, Shana Y.

AU - Lis, Rosina T.

AU - Chun, Guinevere

AU - Gulley, James L.

AU - Merino, Maria J.

AU - Choyke, Peter L.

AU - Ye, Huihui

AU - Dahut, William L.

AU - Turkbey, Baris

AU - Sowalsky, Adam G.

PY - 2020/12/1

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N2 - 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.

AB - 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.

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

Abstract

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ASJC Scopus subject areas

UN SDGs

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