PMID- 29100361 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220311 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 8 IP - 44 DP - 2017 Sep 29 TI - Glyoxalase 1 copy number variation in patients with well differentiated gastro-entero-pancreatic neuroendocrine tumours (GEP-NET). PG - 76961-76973 LID - 10.18632/oncotarget.20290 [doi] AB - 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. FAU - Xue, Mingzhan AU - Xue M AD - Division of Translational Medicine, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital, Coventry, U.K. FAU - Shafie, Alaa AU - Shafie A AD - Division of Translational Medicine, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital, Coventry, U.K. AD - Faculty of Applied Medical Sciences, Taif University, Taif, Kingdom of Saudi Arabia. FAU - Qaiser, Talha AU - Qaiser T AD - Department of Computer Sciences, University of Warwick, Coventry, U.K. FAU - Rajpoot, Nasir M AU - Rajpoot NM AD - Department of Computer Sciences, University of Warwick, Coventry, U.K. FAU - Kaltsas, Gregory AU - Kaltsas G AD - University Hospitals Coventry & Warwickshire NHS Trust, The ARDEN NET Centre, ENETS CoE, Coventry, U.K. FAU - James, Sean AU - James S AD - University Hospitals Coventry & Warwickshire NHS Trust, The ARDEN NET Centre, ENETS CoE, Coventry, U.K. FAU - Gopalakrishnan, Kishore AU - Gopalakrishnan K AD - University Hospitals Coventry & Warwickshire NHS Trust, The ARDEN NET Centre, ENETS CoE, Coventry, U.K. FAU - Fisk, Adrian AU - Fisk A AD - University Hospitals Coventry & Warwickshire NHS Trust, The ARDEN NET Centre, ENETS CoE, Coventry, U.K. FAU - Dimitriadis, Georgios K AU - Dimitriadis GK AD - Division of Translational Medicine, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital, Coventry, U.K. AD - University Hospitals Coventry & Warwickshire NHS Trust, The ARDEN NET Centre, ENETS CoE, Coventry, U.K. AD - Coventry University, Centre for Applied Biological & Exercise Sciences, Coventry, U.K. FAU - Grammatopoulos, Dimitris K AU - Grammatopoulos DK AD - Division of Translational Medicine, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital, Coventry, U.K. AD - University Hospitals Coventry & Warwickshire NHS Trust, The ARDEN NET Centre, ENETS CoE, Coventry, U.K. FAU - Rabbani, Naila AU - Rabbani N AD - Division of Translational Medicine, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital, Coventry, U.K. AD - Warwick Systems Biology Centre, Senate House, University of Warwick, Coventry, U.K. FAU - Thornalley, Paul J AU - Thornalley PJ AD - Division of Translational Medicine, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital, Coventry, U.K. AD - Warwick Systems Biology Centre, Senate House, University of Warwick, Coventry, U.K. FAU - Weickert, Martin O AU - Weickert MO AD - Division of Translational Medicine, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital, Coventry, U.K. AD - University Hospitals Coventry & Warwickshire NHS Trust, The ARDEN NET Centre, ENETS CoE, Coventry, U.K. AD - Coventry University, Centre for Applied Biological & Exercise Sciences, Coventry, U.K. LA - eng PT - Journal Article DEP - 20170816 PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 PMC - PMC5652755 OTO - NOTNLM OT - Glyoxalase OT - copy number variation OT - gastro-entero-pancreatic neuroendocrine tumour OT - glycation OT - multi-drug resistance COIS- CONFLICTS OF INTEREST The authors confirm that there were no conflicts of interest. EDAT- 2017/11/05 06:00 MHDA- 2017/11/05 06:01 PMCR- 2017/09/29 CRDT- 2017/11/05 06:00 PHST- 2016/10/11 00:00 [received] PHST- 2017/06/27 00:00 [accepted] PHST- 2017/11/05 06:00 [entrez] PHST- 2017/11/05 06:00 [pubmed] PHST- 2017/11/05 06:01 [medline] PHST- 2017/09/29 00:00 [pmc-release] AID - 20290 [pii] AID - 10.18632/oncotarget.20290 [doi] PST - epublish SO - Oncotarget. 2017 Aug 16;8(44):76961-76973. doi: 10.18632/oncotarget.20290. eCollection 2017 Sep 29.