title: Gene methylation profile of gastric cancerous tissue according to tumor site in the stomach.
abstract: BACKGROUND
  There is considerable information on the methylation of the promoter regions of different genes involved in gastric carcinogenesis. However, there is a lack of information on how this epigenetic process differs in tumors originating at different sites in the stomach. The aim of this study is to assess the methylation profiles of the MLH1, MGMT, and DAPK-1 genes in cancerous tissues from different stomach sites.
  
  
  METHODS
  Samples were acquired from 81 patients suffering stomach adenocarcinoma who underwent surgery for gastric cancer in the Lithuanian University of Health Sciences Hospital Kaunas Clinics in 2009-2012. Gene methylation was investigated with methylation-specific PCR. The study was approved by the Lithuanian Biomedical Research Ethics Committee.
  
  
  RESULTS
  The frequencies of methylation in cancerous tissues from the upper, middle, and lower thirds of the stomach were 11.1, 23.1, and 45.4%, respectively, for MLH1; 22.2, 30.8, and 57.6%, respectively, for MGMT; and 44.4, 48.7, and 51.5%, respectively, for DAPK-1. MLH1 and MGMT methylation was observed more often in the lower third of the stomach than in the upper third (p < 0.05). In the middle third, DAPK-1 promoter methylation was related to more-advanced disease in the lymph nodes (N2-3 compared with N0-1 [p = 0.02]) and advanced tumor stage (stage III rather than stages I-II [p = 0.05]). MLH1 and MGMT methylation correlated inversely when the tumor was located in the lower third of the stomach (coefficient, -0.48; p = 0.01). DAPK-1 and MLH1 methylation correlated inversely in tumors in the middle-third of the stomach (coefficient, -0.41; p = 0.01).
  
  
  CONCLUSIONS
  Gene promoter methylation depends on the gastric tumor location.
authors.affiliation: Oncology Institute of the Lithuanian University of Health Sciences, Eiveniu 2, Kaunas, 50009, Lithuania. rita.kupcinskaite@gmail.com.
authors.forename: Rita
authors.initials: R
authors.lastname: Kupcinskaite-Noreikiene
authors.affiliation: Oncology Institute of the Lithuanian University of Health Sciences, Eiveniu 2, Kaunas, 50009, Lithuania.
authors.forename: Rasa
authors.initials: R
authors.lastname: Ugenskiene
authors.affiliation: Kaunas University of Technology, Studentu 50, Kaunas, 50009, Lithuania.
authors.forename: Alius
authors.initials: A
authors.lastname: Noreika
authors.affiliation: Oncology Institute of the Lithuanian University of Health Sciences, Eiveniu 2, Kaunas, 50009, Lithuania.
authors.forename: Viktoras
authors.initials: V
authors.lastname: Rudzianskas
authors.affiliation: Oncology Institute of the Lithuanian University of Health Sciences, Eiveniu 2, Kaunas, 50009, Lithuania.
authors.forename: Jurgita
authors.initials: J
authors.lastname: Gedminaite
authors.affiliation: Laboratory of Clinical and Molecular Gastroenterology, Lithuanian University of Health Sciences, Eiveniu 2, Kaunas, 50009, Lithuania.
authors.forename: Jurgita
authors.initials: J
authors.lastname: Skieceviciene
authors.affiliation: Oncology Institute of the Lithuanian University of Health Sciences, Eiveniu 2, Kaunas, 50009, Lithuania.
authors.forename: Elona
authors.initials: E
authors.lastname: Juozaityte
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D064550:Death-Associated Protein Kinases / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases; D000070957:MutL Protein Homolog 1; D045643:DNA Repair Enzymes
references.citation: Lab Invest. 2003 Apr;83(4):519-26
references.pmid: 12695555
references.citation: Am J Pathol. 2003 Oct;163(4):1551-6
references.pmid: 14507661
references.citation: Anticancer Res. 2009 Dec;29(12):5053-5
references.pmid: 20044616
references.citation: Int J Cancer. 2000 Jul 15;87(2):200-3
references.pmid: 10861474
references.citation: Lancet. 1975 Jul 12;2(7924):58-60
references.pmid: 49653
references.citation: Cancer Lett. 2011 Dec 1;311(1):85-95
references.pmid: 21831520
references.citation: J Surg Oncol. 2011 Jun 1;103(7):687-94
references.pmid: 21308683
references.citation: Acta Pathol Microbiol Scand. 1965;64:31-49
references.pmid: 14320675
references.citation: Epigenomics. 2012 Jun;4(3):279-94
references.pmid: 22690664
references.citation: Helicobacter. 2008 Feb;13(1):35-41
references.pmid: 18205664
references.citation: Tumori. 2010 Sep-Oct;96(5):726-33
references.pmid: 21302620
references.citation: Gastroenterol Clin North Am. 2000 Sep;29(3):559-78
references.pmid: 11030073
references.citation: Anticancer Res. 2010 Jan;30(1):239-44
references.pmid: 20150642
references.citation: World J Gastroenterol. 2006 Jan 21;12(3):354-62
references.pmid: 16489633
references.citation: Trends Genet. 1997 Nov;13(11):444-9
references.pmid: 9385841
references.citation: World J Gastroenterol. 2013 May 28;19(20):3043-51
references.pmid: 23716983
references.citation: J Korean Med Sci. 2005 Apr;20(2):236-41
references.pmid: 15831994
references.citation: Oncol Rep. 2011 Feb;25(2):513-8
references.pmid: 21152877
references.citation: Pathobiology. 2011;78(5):266-76
references.pmid: 21849808
references.citation: Clin Chim Acta. 2009 Jun 27;404(2):128-33
references.pmid: 19336228
references.citation: Biocell. 2008 Dec;32(3):237-43
references.pmid: 19181186
references.citation: J Pathol. 2004 Jun;203(2):681-7
references.pmid: 15141383
references.citation: Int J Cancer. 2008 Feb 1;122(3):603-8
references.pmid: 17943730
references.citation: Medicina (Kaunas). 2013;49(8):361-6
references.pmid: 24509146
references.citation: Gastric Cancer. 2015 Apr;18(2):280-7
references.pmid: 24748501
references.citation: Eur J Cancer. 2003 Jun;39(9):1222-7
references.pmid: 12763209
references.citation: Cancer. 2001 Dec 1;92(11):2760-8
references.pmid: 11753949
references.citation: JAMA. 1991 Mar 13;265(10):1287-9
references.pmid: 1995976
references.citation: Pathobiology. 2001;69(3):143-9
references.pmid: 11872960
references.citation: N Engl J Med. 2001 Sep 13;345(11):784-9
references.pmid: 11556297
references.citation: World J Gastroenterol. 2010 Jan 21;16(3):312-9
references.pmid: 20082476
references.citation: Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):656-63
references.pmid: 15701853
references.citation: Anticancer Res. 2009 Oct;29(10):3759-68
references.pmid: 19846906
references.citation: Eur J Cancer Prev. 2012 May;21(3):241-6
references.pmid: 21979297
references.citation: Digestion. 2006;74(2):85-90
references.pmid: 17139167
references.citation: Am J Gastroenterol. 2007 Jul;102(7):1361-71
references.pmid: 17509026
references.citation: Am J Cancer Res. 2012;2(1):116-29
references.pmid: 22206050
references.citation: Ann Surg Oncol. 2010 Apr;17(4):1177-86
references.pmid: 19957042
references.citation: Adv Genet. 2010;70:27-56
references.pmid: 20920744