Cargando…

Glyoxalase 1 copy number variation in patients with well differentiated gastro-entero-pancreatic neuroendocrine tumours (GEP-NET)

BACKGROUND: The glyoxalase-1 gene (GLO1) is a hotspot for copy-number variation (CNV) in human genomes. Increased GLO1 copy-number is associated with multidrug resistance in tumour chemotherapy, but prevalence of GLO1 CNV in gastro-entero-pancreatic neuroendocrine tumours (GEP-NET) is unknown. METHO...

Descripción completa

Detalles Bibliográficos
Autores principales: Xue, Mingzhan, Shafie, Alaa, Qaiser, Talha, Rajpoot, Nasir M., Kaltsas, Gregory, James, Sean, Gopalakrishnan, Kishore, Fisk, Adrian, Dimitriadis, Georgios K., Grammatopoulos, Dimitris K., Rabbani, Naila, Thornalley, Paul J., Weickert, Martin O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652755/
https://www.ncbi.nlm.nih.gov/pubmed/29100361
http://dx.doi.org/10.18632/oncotarget.20290
_version_ 1783273120507887616
author Xue, Mingzhan
Shafie, Alaa
Qaiser, Talha
Rajpoot, Nasir M.
Kaltsas, Gregory
James, Sean
Gopalakrishnan, Kishore
Fisk, Adrian
Dimitriadis, Georgios K.
Grammatopoulos, Dimitris K.
Rabbani, Naila
Thornalley, Paul J.
Weickert, Martin O.
author_facet Xue, Mingzhan
Shafie, Alaa
Qaiser, Talha
Rajpoot, Nasir M.
Kaltsas, Gregory
James, Sean
Gopalakrishnan, Kishore
Fisk, Adrian
Dimitriadis, Georgios K.
Grammatopoulos, Dimitris K.
Rabbani, Naila
Thornalley, Paul J.
Weickert, Martin O.
author_sort Xue, Mingzhan
collection PubMed
description BACKGROUND: The glyoxalase-1 gene (GLO1) is a hotspot for copy-number variation (CNV) in human genomes. Increased GLO1 copy-number is associated with multidrug resistance in tumour chemotherapy, but prevalence of GLO1 CNV in gastro-entero-pancreatic neuroendocrine tumours (GEP-NET) is unknown. METHODS: GLO1 copy-number variation was measured in 39 patients with GEP-NET (midgut NET, n = 25; pancreatic NET, n = 14) after curative or debulking surgical treatment. Primary tumour tissue, surrounding healthy tissue and, where applicable, additional metastatic tumour tissue were analysed, using real time qPCR. Progression and survival following surgical treatment were monitored over 4.2 ± 0.5 years. RESULTS: In the pooled GEP-NET cohort, GLO1 copy-number in healthy tissue was 2.0 in all samples but significantly increased in primary tumour tissue in 43% of patients with pancreatic NET and in 72% of patients with midgut NET, mainly driven by significantly higher GLO1 copy-number in midgut NET. In tissue from additional metastases resection (18 midgut NET and one pancreatic NET), GLO1 copy number was also increased, compared with healthy tissue; but was not significantly different compared with primary tumour tissue. During mean 3 - 5 years follow-up, 8 patients died and 16 patients showed radiological progression. In midgut NET, a high GLO1 copy-number was associated with earlier progression. In NETs with increased GLO1 copy number, there was increased Glo1 protein expression compared to non-malignant tissue. CONCLUSIONS: GLO1 copy-number was increased in a large percentage of patients with GEP-NET and correlated positively with increased Glo1 protein in tumour tissue. Analysis of GLO1 copy-number variation particularly in patients with midgut NET could be a novel prognostic marker for tumour progression.
format Online
Article
Text
id pubmed-5652755
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-56527552017-11-02 Glyoxalase 1 copy number variation in patients with well differentiated gastro-entero-pancreatic neuroendocrine tumours (GEP-NET) Xue, Mingzhan Shafie, Alaa Qaiser, Talha Rajpoot, Nasir M. Kaltsas, Gregory James, Sean Gopalakrishnan, Kishore Fisk, Adrian Dimitriadis, Georgios K. Grammatopoulos, Dimitris K. Rabbani, Naila Thornalley, Paul J. Weickert, Martin O. Oncotarget Research Paper BACKGROUND: The glyoxalase-1 gene (GLO1) is a hotspot for copy-number variation (CNV) in human genomes. Increased GLO1 copy-number is associated with multidrug resistance in tumour chemotherapy, but prevalence of GLO1 CNV in gastro-entero-pancreatic neuroendocrine tumours (GEP-NET) is unknown. METHODS: GLO1 copy-number variation was measured in 39 patients with GEP-NET (midgut NET, n = 25; pancreatic NET, n = 14) after curative or debulking surgical treatment. Primary tumour tissue, surrounding healthy tissue and, where applicable, additional metastatic tumour tissue were analysed, using real time qPCR. Progression and survival following surgical treatment were monitored over 4.2 ± 0.5 years. RESULTS: In the pooled GEP-NET cohort, GLO1 copy-number in healthy tissue was 2.0 in all samples but significantly increased in primary tumour tissue in 43% of patients with pancreatic NET and in 72% of patients with midgut NET, mainly driven by significantly higher GLO1 copy-number in midgut NET. In tissue from additional metastases resection (18 midgut NET and one pancreatic NET), GLO1 copy number was also increased, compared with healthy tissue; but was not significantly different compared with primary tumour tissue. During mean 3 - 5 years follow-up, 8 patients died and 16 patients showed radiological progression. In midgut NET, a high GLO1 copy-number was associated with earlier progression. In NETs with increased GLO1 copy number, there was increased Glo1 protein expression compared to non-malignant tissue. CONCLUSIONS: GLO1 copy-number was increased in a large percentage of patients with GEP-NET and correlated positively with increased Glo1 protein in tumour tissue. Analysis of GLO1 copy-number variation particularly in patients with midgut NET could be a novel prognostic marker for tumour progression. Impact Journals LLC 2017-08-16 /pmc/articles/PMC5652755/ /pubmed/29100361 http://dx.doi.org/10.18632/oncotarget.20290 Text en Copyright: © 2017 Xue et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Xue, Mingzhan
Shafie, Alaa
Qaiser, Talha
Rajpoot, Nasir M.
Kaltsas, Gregory
James, Sean
Gopalakrishnan, Kishore
Fisk, Adrian
Dimitriadis, Georgios K.
Grammatopoulos, Dimitris K.
Rabbani, Naila
Thornalley, Paul J.
Weickert, Martin O.
Glyoxalase 1 copy number variation in patients with well differentiated gastro-entero-pancreatic neuroendocrine tumours (GEP-NET)
title Glyoxalase 1 copy number variation in patients with well differentiated gastro-entero-pancreatic neuroendocrine tumours (GEP-NET)
title_full Glyoxalase 1 copy number variation in patients with well differentiated gastro-entero-pancreatic neuroendocrine tumours (GEP-NET)
title_fullStr Glyoxalase 1 copy number variation in patients with well differentiated gastro-entero-pancreatic neuroendocrine tumours (GEP-NET)
title_full_unstemmed Glyoxalase 1 copy number variation in patients with well differentiated gastro-entero-pancreatic neuroendocrine tumours (GEP-NET)
title_short Glyoxalase 1 copy number variation in patients with well differentiated gastro-entero-pancreatic neuroendocrine tumours (GEP-NET)
title_sort glyoxalase 1 copy number variation in patients with well differentiated gastro-entero-pancreatic neuroendocrine tumours (gep-net)
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652755/
https://www.ncbi.nlm.nih.gov/pubmed/29100361
http://dx.doi.org/10.18632/oncotarget.20290
work_keys_str_mv AT xuemingzhan glyoxalase1copynumbervariationinpatientswithwelldifferentiatedgastroenteropancreaticneuroendocrinetumoursgepnet
AT shafiealaa glyoxalase1copynumbervariationinpatientswithwelldifferentiatedgastroenteropancreaticneuroendocrinetumoursgepnet
AT qaisertalha glyoxalase1copynumbervariationinpatientswithwelldifferentiatedgastroenteropancreaticneuroendocrinetumoursgepnet
AT rajpootnasirm glyoxalase1copynumbervariationinpatientswithwelldifferentiatedgastroenteropancreaticneuroendocrinetumoursgepnet
AT kaltsasgregory glyoxalase1copynumbervariationinpatientswithwelldifferentiatedgastroenteropancreaticneuroendocrinetumoursgepnet
AT jamessean glyoxalase1copynumbervariationinpatientswithwelldifferentiatedgastroenteropancreaticneuroendocrinetumoursgepnet
AT gopalakrishnankishore glyoxalase1copynumbervariationinpatientswithwelldifferentiatedgastroenteropancreaticneuroendocrinetumoursgepnet
AT fiskadrian glyoxalase1copynumbervariationinpatientswithwelldifferentiatedgastroenteropancreaticneuroendocrinetumoursgepnet
AT dimitriadisgeorgiosk glyoxalase1copynumbervariationinpatientswithwelldifferentiatedgastroenteropancreaticneuroendocrinetumoursgepnet
AT grammatopoulosdimitrisk glyoxalase1copynumbervariationinpatientswithwelldifferentiatedgastroenteropancreaticneuroendocrinetumoursgepnet
AT rabbaninaila glyoxalase1copynumbervariationinpatientswithwelldifferentiatedgastroenteropancreaticneuroendocrinetumoursgepnet
AT thornalleypaulj glyoxalase1copynumbervariationinpatientswithwelldifferentiatedgastroenteropancreaticneuroendocrinetumoursgepnet
AT weickertmartino glyoxalase1copynumbervariationinpatientswithwelldifferentiatedgastroenteropancreaticneuroendocrinetumoursgepnet