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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
---|---|
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 |