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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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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 |
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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 |
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