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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 13, 2020
- Source ID
- 10.1038/s41467-020-14657-7
Entities
People
- Adam G Sowalsky
- Baris Turkbey
- David J. VanderWeele
- Fatima Karzai
- Guinevere Chun
- Huihui Ye
- James L. Gulley
- John R. Bright
- Maria J. Merino
- Nicholas T Terrigino
- Nicole V Carrabba
- Peter A. Pinto
- Peter L Choyke
- Ravi A Madan
- Rayann Atway
- Rosina T Lis
- Ross Lake
- Scott Wilkinson
- Shana Y. Trostel
- Stephanie A. Harmon
- William L. Dahut
Organizations
- Congressionally Directed Medical Research Programs
- National Cancer Institute
- Prostate Cancer Foundation
- United States Department of Health and Human Services