Cargando…

PTEN loss in circulating tumour cells correlates with PTEN loss in fresh tumour tissue from castration-resistant prostate cancer patients

BACKGROUND: PTEN gene loss occurs frequently in castration-resistant prostate cancer (CRPC) and may drive progression through activation of the PI3K/AKT pathway. Here, we developed a novel CTC-based assay to determine PTEN status and examined the correlation between PTEN status in CTCs and matched t...

Descripción completa

Detalles Bibliográficos
Autores principales: Punnoose, Elizabeth A, Ferraldeschi, Roberta, Szafer-Glusman, Edith, Tucker, Eric K, Mohan, Sankar, Flohr, Penelope, Riisnaes, Ruth, Miranda, Susana, Figueiredo, Ines, Rodrigues, Daniel Nava, Omlin, Aurelius, Pezaro, Carmel, Zhu, Jin, Amler, Lukas, Patel, Premal, Yan, Yibing, Bales, Natalee, Werner, Shannon L, Louw, Jessica, Pandita, Ajay, Marrinucci, Dena, Attard, Gerhardt, de Bono, Johann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647881/
https://www.ncbi.nlm.nih.gov/pubmed/26379078
http://dx.doi.org/10.1038/bjc.2015.332
_version_ 1782401177689784320
author Punnoose, Elizabeth A
Ferraldeschi, Roberta
Szafer-Glusman, Edith
Tucker, Eric K
Mohan, Sankar
Flohr, Penelope
Riisnaes, Ruth
Miranda, Susana
Figueiredo, Ines
Rodrigues, Daniel Nava
Omlin, Aurelius
Pezaro, Carmel
Zhu, Jin
Amler, Lukas
Patel, Premal
Yan, Yibing
Bales, Natalee
Werner, Shannon L
Louw, Jessica
Pandita, Ajay
Marrinucci, Dena
Attard, Gerhardt
de Bono, Johann
author_facet Punnoose, Elizabeth A
Ferraldeschi, Roberta
Szafer-Glusman, Edith
Tucker, Eric K
Mohan, Sankar
Flohr, Penelope
Riisnaes, Ruth
Miranda, Susana
Figueiredo, Ines
Rodrigues, Daniel Nava
Omlin, Aurelius
Pezaro, Carmel
Zhu, Jin
Amler, Lukas
Patel, Premal
Yan, Yibing
Bales, Natalee
Werner, Shannon L
Louw, Jessica
Pandita, Ajay
Marrinucci, Dena
Attard, Gerhardt
de Bono, Johann
author_sort Punnoose, Elizabeth A
collection PubMed
description BACKGROUND: PTEN gene loss occurs frequently in castration-resistant prostate cancer (CRPC) and may drive progression through activation of the PI3K/AKT pathway. Here, we developed a novel CTC-based assay to determine PTEN status and examined the correlation between PTEN status in CTCs and matched tumour tissue samples. METHODS: PTEN gene status in CTCs was evaluated on an enrichment-free platform (Epic Sciences) by fluorescence in situ hybridisation (FISH). PTEN status in archival and fresh tumour tissue was evaluated by FISH and immunohistochemistry. RESULTS: Peripheral blood was collected from 76 patients. Matched archival and fresh cancer tissue was available for 48 patients. PTEN gene status detected in CTCs was concordant with PTEN status in matched fresh tissues and archival tissue in 32 of 38 patients (84%) and 24 of 39 patients (62%), respectively. CTC counts were prognostic (continuous, P=0.001). PTEN loss in CTCs associated with worse survival in univariate analysis (HR 2.05; 95% CI 1.17–3.62; P=0.01) and with high lactate dehydrogenase (LDH) in metastatic CRPC patients. CONCLUSIONS: Our results illustrate the potential use of CTCs as a non-invasive, real-time liquid biopsy to determine PTEN gene status. The prognostic and predictive value of PTEN in CTCs warrants investigation in CRPC clinical trials of PI3K/AKT-targeted therapies.
format Online
Article
Text
id pubmed-4647881
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-46478812015-12-01 PTEN loss in circulating tumour cells correlates with PTEN loss in fresh tumour tissue from castration-resistant prostate cancer patients Punnoose, Elizabeth A Ferraldeschi, Roberta Szafer-Glusman, Edith Tucker, Eric K Mohan, Sankar Flohr, Penelope Riisnaes, Ruth Miranda, Susana Figueiredo, Ines Rodrigues, Daniel Nava Omlin, Aurelius Pezaro, Carmel Zhu, Jin Amler, Lukas Patel, Premal Yan, Yibing Bales, Natalee Werner, Shannon L Louw, Jessica Pandita, Ajay Marrinucci, Dena Attard, Gerhardt de Bono, Johann Br J Cancer Molecular Diagnostics BACKGROUND: PTEN gene loss occurs frequently in castration-resistant prostate cancer (CRPC) and may drive progression through activation of the PI3K/AKT pathway. Here, we developed a novel CTC-based assay to determine PTEN status and examined the correlation between PTEN status in CTCs and matched tumour tissue samples. METHODS: PTEN gene status in CTCs was evaluated on an enrichment-free platform (Epic Sciences) by fluorescence in situ hybridisation (FISH). PTEN status in archival and fresh tumour tissue was evaluated by FISH and immunohistochemistry. RESULTS: Peripheral blood was collected from 76 patients. Matched archival and fresh cancer tissue was available for 48 patients. PTEN gene status detected in CTCs was concordant with PTEN status in matched fresh tissues and archival tissue in 32 of 38 patients (84%) and 24 of 39 patients (62%), respectively. CTC counts were prognostic (continuous, P=0.001). PTEN loss in CTCs associated with worse survival in univariate analysis (HR 2.05; 95% CI 1.17–3.62; P=0.01) and with high lactate dehydrogenase (LDH) in metastatic CRPC patients. CONCLUSIONS: Our results illustrate the potential use of CTCs as a non-invasive, real-time liquid biopsy to determine PTEN gene status. The prognostic and predictive value of PTEN in CTCs warrants investigation in CRPC clinical trials of PI3K/AKT-targeted therapies. Nature Publishing Group 2015-10-20 2015-09-17 /pmc/articles/PMC4647881/ /pubmed/26379078 http://dx.doi.org/10.1038/bjc.2015.332 Text en Copyright © 2015 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under the Creative Commons Attribution-Non-Commercial-Share Alike 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Molecular Diagnostics
Punnoose, Elizabeth A
Ferraldeschi, Roberta
Szafer-Glusman, Edith
Tucker, Eric K
Mohan, Sankar
Flohr, Penelope
Riisnaes, Ruth
Miranda, Susana
Figueiredo, Ines
Rodrigues, Daniel Nava
Omlin, Aurelius
Pezaro, Carmel
Zhu, Jin
Amler, Lukas
Patel, Premal
Yan, Yibing
Bales, Natalee
Werner, Shannon L
Louw, Jessica
Pandita, Ajay
Marrinucci, Dena
Attard, Gerhardt
de Bono, Johann
PTEN loss in circulating tumour cells correlates with PTEN loss in fresh tumour tissue from castration-resistant prostate cancer patients
title PTEN loss in circulating tumour cells correlates with PTEN loss in fresh tumour tissue from castration-resistant prostate cancer patients
title_full PTEN loss in circulating tumour cells correlates with PTEN loss in fresh tumour tissue from castration-resistant prostate cancer patients
title_fullStr PTEN loss in circulating tumour cells correlates with PTEN loss in fresh tumour tissue from castration-resistant prostate cancer patients
title_full_unstemmed PTEN loss in circulating tumour cells correlates with PTEN loss in fresh tumour tissue from castration-resistant prostate cancer patients
title_short PTEN loss in circulating tumour cells correlates with PTEN loss in fresh tumour tissue from castration-resistant prostate cancer patients
title_sort pten loss in circulating tumour cells correlates with pten loss in fresh tumour tissue from castration-resistant prostate cancer patients
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647881/
https://www.ncbi.nlm.nih.gov/pubmed/26379078
http://dx.doi.org/10.1038/bjc.2015.332
work_keys_str_mv AT punnooseelizabetha ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT ferraldeschiroberta ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT szaferglusmanedith ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT tuckererick ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT mohansankar ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT flohrpenelope ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT riisnaesruth ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT mirandasusana ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT figueiredoines ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT rodriguesdanielnava ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT omlinaurelius ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT pezarocarmel ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT zhujin ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT amlerlukas ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT patelpremal ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT yanyibing ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT balesnatalee ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT wernershannonl ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT louwjessica ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT panditaajay ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT marrinuccidena ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT attardgerhardt ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients
AT debonojohann ptenlossincirculatingtumourcellscorrelateswithptenlossinfreshtumourtissuefromcastrationresistantprostatecancerpatients