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

2 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

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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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), [837]. https://doi.org/10.1038/s41467-020-14657-7

Wilkinson, Scott ; Harmon, Stephanie A. ; Terrigino, Nicholas T. ; Karzai, Fatima ; Pinto, Peter A. ; Madan, Ravi A. ; VanderWeele, David J. ; Lake, Ross ; Atway, Rayann ; Bright, John R. ; Carrabba, Nicole V. ; Trostel, Shana Y. ; Lis, Rosina T. ; Chun, Guinevere ; Gulley, James L. ; Merino, Maria J. ; Choyke, Peter L. ; Ye, Huihui ; Dahut, William L. ; Turkbey, Baris ; Sowalsky, Adam G. / A case report of multiple primary prostate tumors with differential drug sensitivity. In: Nature communications. 2020 ; Vol. 11, No. 1.

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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.",

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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

A case report of multiple primary prostate tumors with differential drug sensitivity. / Wilkinson, Scott; Harmon, Stephanie A.; Terrigino, Nicholas T.; Karzai, Fatima; Pinto, Peter A.; Madan, Ravi A.; VanderWeele, David J.; Lake, Ross; Atway, Rayann; Bright, John R.; Carrabba, Nicole V.; Trostel, Shana Y.; Lis, Rosina T.; Chun, Guinevere; Gulley, James L.; Merino, Maria J.; Choyke, Peter L.; Ye, Huihui; Dahut, William L.; Turkbey, Baris; Sowalsky, Adam G.

In: Nature communications, Vol. 11, No. 1, 837, 01.12.2020.

Research output: Contribution to journal › Article

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AU - Wilkinson, Scott

AU - Harmon, Stephanie A.

AU - Terrigino, Nicholas T.

AU - Karzai, Fatima

AU - Pinto, Peter A.

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.

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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.

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