Review
Copyright ©The Author(s) 2017.
World J Gastrointest Oncol. Sep 15, 2017; 9(9): 341-353
Published online Sep 15, 2017. doi: 10.4251/wjgo.v9.i9.341
Table 2 Methylation profiles in neuroendocrine tumors
ModificationGeneGene functionClinical effectTumorRef.
Hypermethylation (Inactivation)
RASSF1Induces cell cycle arrestCorrelated with malignancy, levels highest in metastasesPNET > GI-NET[32-34]
INK4a/p16Induces cell cycle arrest and apoptosisDecreased 5-yr survival, liver metastasesPNET, gastrinoma[38,39]
MGMTDNA repairImproved response to temozolomidePNET[32]
TIMP-3Inhibits metalloproteinasesCorrelated with metastasesPNET[44]
UCHL-1Post-translational modifier, de-ubiquitinates proteins marked for lysosomal degradationCorrelated with metastasesGEP-NET[45-47]
IGF2Chromatin packagingSpecific for insulinomas, increased stageInsulinoma[51]
MLH1DNA repairCorrelated with malignancyPNET, insulinoma[52]
Global hypomethylation
LINE-1Repeating long interspersed nucleotide elementsCorrelated with malignancy and lymph node metastasesIleal NET > GEP-NET[53-55]
AluRepeating long interspersed nucleotide elementsCorrelated with malignancyGEP-NET[54]