Abstract

Neuroendocrine prostate cancer is an aggressive variant of prostate cancer that may arise de novo or develop from pre-existing prostate adenocarcinoma as a mechanism of treatment resistance. The combined loss of tumor suppressors RB1, TP53, and PTEN are frequent in NEPC but also present in a subset of prostate adenocarcinomas. Most clinical and preclinical studies support a trans-differentiation process, whereby NEPC arises clonally from a prostate adenocarcinoma precursor during the course of treatment resistance. Here we highlight a case of NEPC with significant intra-patient heterogeneity observed across metastases. We further demonstrate how single-cell genomic analysis of circulating tumor cells combined with a phenotypic evaluation of cellular diversity can be considered as a window into tumor heterogeneity in patients with advanced prostate cancer.

Details

Title
Circulating tumor cell heterogeneity in neuroendocrine prostate cancer by single cell copy number analysis
Author
Conteduca Vincenza 1   VIAFID ORCID Logo  ; Sheng-Yu, Ku 2 ; Fernandez, Luisa 3 ; Dago-Rodriquez Angel 3 ; Lee, Jerry 3 ; Jendrisak Adam 3 ; Slade, Megan 3 ; Gilbertson Cole 3 ; Manohar Jyothi 4 ; Sigouros, Michael 4   VIAFID ORCID Logo  ; Wang, Yipeng 3 ; Ryan, Dittamore 3 ; Wenstrup, Rick 3 ; Mosquera, Juan Miguel 4   VIAFID ORCID Logo  ; Schonhoft, Joseph D 3 ; Beltran Himisha 5   VIAFID ORCID Logo 

1  Dana Farber Cancer Institute and Harvard Medical School, Boston, USA (GRID:grid.65499.37) (ISNI:0000 0001 2106 9910); IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy (GRID:grid.65499.37) 
2  Dana Farber Cancer Institute and Harvard Medical School, Boston, USA (GRID:grid.65499.37) (ISNI:0000 0001 2106 9910) 
3  Epic Sciences, Inc., San Diego, USA (GRID:grid.509720.9) 
4  Weill Cornell Medicine, New York, USA (GRID:grid.5386.8) (ISNI:000000041936877X) 
5  Dana Farber Cancer Institute and Harvard Medical School, Boston, USA (GRID:grid.65499.37) (ISNI:0000 0001 2106 9910); Weill Cornell Medicine, New York, USA (GRID:grid.5386.8) (ISNI:000000041936877X) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
ISSN
2397768X
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41698-021-00211-1
ProQuest document ID
2560479291
Copyright
© The Author(s) 2021. corrected publication 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.