Publikation

Tumor clone dynamics in lethal prostate cancer

Wissenschaftlicher Artikel/Review - 17.09.2014

Bereiche
PubMed
DOI

Zitation
Carreira S, Demichelis F, S de Bono J, Tunariu N, Flohr P, Rodrigues D, Omlin A, Pezaro C, Frenel J, Lorente D, Prandi D, Miranda S, Ferraldeschi R, Grist E, Goodall J, Romanel A, Attard G. Tumor clone dynamics in lethal prostate cancer. Sci Transl Med 2014; 6:254ra125.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Sci Transl Med 2014; 6
Veröffentlichungsdatum
17.09.2014
eISSN (Online)
1946-6242
Seiten
254ra125
Kurzbeschreibung/Zielsetzung

It is unclear whether a single clone metastasizes and remains dominant over the course of lethal prostate cancer. We describe the clonal architectural heterogeneity at different stages of disease progression by sequencing serial plasma and tumor samples from 16 ERG-positive patients. By characterizing the clonality of commonly occurring deletions at 21q22, 8p21, and 10q23, we identified multiple independent clones in metastatic disease that are differentially represented in tissue and circulation. To exemplify the clinical utility of our studies, we then showed a temporal association between clinical progression and emergence of androgen receptor (AR) mutations activated by glucocorticoids in about 20% of patients progressing on abiraterone and prednisolone or dexamethasone. Resistant clones showed a complex dynamic with temporal and spatial heterogeneity, suggesting distinct mechanisms of resistance at different sites that emerged and regressed depending on treatment selection pressure. This introduces a management paradigm requiring sequential monitoring of advanced prostate cancer patients with plasma and tumor biopsies to ensure early discontinuation of agents when they become potential disease drivers.