Journal Article

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

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

2020

Overview

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. Prostate cancer is often a multifocal disease but how best to manage this clinically remains unclear. Here, the authors report a single case study of a patient with two genetically diverse tumours which showed differential response to therapy.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/51 / 45/22 / 45/23 / 45/77 / 49/23 / 59/57 / 631/67/2329 / 631/67/589/466 / 631/67/69 / 692/4028/67/2321 / 692/53/2421 / 82/51 / Ablation / Aged / Androgen Antagonists - therapeutic use / Case reports / Deprivation / Disease control / DNA sequencing / Drug Resistance, Neoplasm / Gene Deletion / Humanities and Social Sciences / Humans / Male / multidisciplinary / Mutation / Neoadjuvant Therapy / Neoplasm Grading / Neoplasms, Multiple Primary - drug therapy / Neoplasms, Multiple Primary - genetics / Neoplasms, Multiple Primary - pathology / p53 Protein / Patients / Prostate cancer / Prostatic Neoplasms - drug therapy / Prostatic Neoplasms - genetics / Prostatic Neoplasms - pathology / PTEN Phosphohydrolase - deficiency / PTEN Phosphohydrolase - genetics / PTEN protein / Science / Science (multidisciplinary) / Sequence Analysis, DNA / Therapy / Treatment resistance / Tumor Suppressor Protein p53 - deficiency / Tumor Suppressor Protein p53 - genetics / Tumors / Variability