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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

Nature communications, 2020-02, Vol.11 (1), p.837-8, Article 837 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
A case report of multiple primary prostate tumors with differential drug sensitivity
Autor: 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
Assuntos: Ablation ; Aged ; Androgen Antagonists - therapeutic use ; Case reports ; Deprivation ; Disease control ; DNA sequencing ; Drug Resistance, Neoplasm ; Gene Deletion ; Humans ; Male ; 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 ; Sequence Analysis, DNA ; Therapy ; Tumor Suppressor Protein p53 - deficiency ; Tumor Suppressor Protein p53 - genetics ; Tumors ; Variability
É parte de: Nature communications, 2020-02, Vol.11 (1), p.837-8, Article 837
Descrição: 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.
Editor: England: Nature Publishing Group
Idioma: Inglês

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

England: Nature Publishing Group

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