title: Site- and grade-specific diversity of LINE1 methylation pattern in gastroenteropancreatic neuroendocrine tumours.
abstract: BACKGROUND
  Recent data indicate that gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have a hypomethylated long interspersed element (LINE1) promoter. To answer the question, of whether LINE1 may be of value in assessing the malignant potential of GEP-NETs, we analysed LINE1 methylation in different organs.
  
  
  METHODS
  A total of 58 GEP-NETs of gastric (n=14), pancreatic (n=15), small intestine (n=17), appendix (n=8), colorectal (n=4) and non-neoplastic tissues were analysed using DNA isolation, bisulphite-treatment and pyrosequencing.
  
  
  RESULTS
  LINE1 hypomethylation was detected in 50% of gastric, 100% pancreatic, 82% small intestine, 87.5% appendix and 100% colorectal NETs. G1 (p<0.001) and G2 (p<0.05) colorectal, and G1 (p<0.001) and G2 (p<0.001) pancreatic NETs exhibited significant LINE1 hypomethylation compared with non-neoplastic tissues. Higher rates of LINE1 hypomethylation in G2 pancreatic NETs than in G1 NETs (p<0.05) were observed. NETs exhibited a significantly lower frequency of hypomethylation in cases with lymph node metastases (p<0.05).
  
  
  CONCLUSIONS
  LINE1 hypomethylation may serve as a marker of tumour grade and lymph node metastasis.
authors.affiliation: Institute of Pathology, Ruhr University Bochum, Bochum, Germany. ingo.stricker@ruhr-unibochum.de
authors.forename: Ingo
authors.initials: I
authors.lastname: Stricker
authors.forename: Dimitri
authors.initials: D
authors.lastname: Tzivras
authors.forename: Sandeep
authors.initials: S
authors.lastname: Nambiar
authors.forename: Juergen
authors.initials: J
authors.lastname: Wulf
authors.forename: Sven-Thorsten
authors.initials: ST
authors.lastname: Liffers
authors.forename: Markus
authors.initials: M
authors.lastname: Vogt
authors.forename: Berlinda
authors.initials: B
authors.lastname: Verdoodt
authors.forename: Andrea
authors.initials: A
authors.lastname: Tannapfel
authors.forename: Alireza
authors.initials: A
authors.lastname: Mirmohammadsadegh
mesh_terms: D015331:Cohort Studies; D019175:DNA Methylation; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016612:Paraffin Embedding