A case report of multiple primary prostate tumors with differential drug sensitivity
© 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply. 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.
Wilkinson, S., Harmon, S., Terrigino, N., Karzai, F., Pinto, P., Madan, R., VanderWeele, D., Lake, R., Atway, R., Bright, J., Carrabba, N., Trostel, S., Lis, R., Chun, G., Gulley, J., Merino, M., Choyke, P., Ye, H., Dahut, W., Turkbey, B., & Sowalsky, A. (2020). A case report of multiple primary prostate tumors with differential drug sensitivity. Nature Communications, 11 (1). http://dx.doi.org/10.1038/s41467-020-14657-7