RGD Reference Report - Robust quantitative assessments of cytosine modifications and changes in the expressions of related enzymes in gastric cancer. - Rat Genome Database

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Robust quantitative assessments of cytosine modifications and changes in the expressions of related enzymes in gastric cancer.

Authors: Du, Chunping  Kurabe, Nobuya  Matsushima, Yoshitaka  Suzuki, Masako  Kahyo, Tomoaki  Ohnishi, Ippei  Tanioka, Fumihiko  Tajima, Shogo  Goto, Masanori  Yamada, Hidetaka  Tao, Hong  Shinmura, Kazuya  Konno, Hiroyuki  Sugimura, Haruhiko 
Citation: Du C, etal., Gastric Cancer. 2015 Jul;18(3):516-25. doi: 10.1007/s10120-014-0409-4. Epub 2014 Aug 7.
RGD ID: 149735841
Pubmed: PMID:25098926   (View Abstract at PubMed)
DOI: DOI:10.1007/s10120-014-0409-4   (Journal Full-text)


BACKGROUND: The rediscovery of 5-hydroxymethylcytosine, the ten-eleven translocation (TET) family, thymine-DNA glycosylase (TDG) and isocitrate dehydrogenase (IDH) have opened new avenues in the study of DNA demethylation pathways in gastric cancer (GC). We performed a comprehensive and robust analysis of these genes and modified cytosines in gastric cancer.
METHODS: Liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS) was used to assess 5-methyldeoxycytidine (5-mC), 5-hydroxymethyldeoxycytidine (5-hmC), 5-formyldeoxycytidine (5-fC) and 5-carboxyldeoxycytidine (5-caC) quantitatively in tumorous and non-tumorous regions of GCs; [D2]-5-hmC was used as an internal standard. Expression levels of the genes TET1, TET2, TET3, TDG, IDH1 and IDH2 were measured using a real-time reverse transcription polymerase chain reaction (RT-PCR) and were compared to the clinical attributes of each case. Using HEK293T cells the effects of introducing plasmids containing full-length TET1, TET2, and TET3 and 7 variants of the TET2 catalytic domain were evaluated in terms of their effect on cytosine demethylation.
RESULTS: LC-MS/MS showed that 5-hmC was significantly decreased in tumorous portions. 5-mC was also moderately decreased in tumors, while 5-fC and 5-caC were barely detectable. The expressions of TET1, TET2, TET3, TDG and IDH2, but not IDH1, were notably decreased in GCs, compared with the adjacent non-tumor portion. TET1 expression and the 5-hmC levels determined using LC-MS/MS had a significantly positive correlation and TET1 protein had a greater effect on the increase in 5-hmC than TET2 and TET3 in HEK293T cells.
CONCLUSIONS: The loss of 5-hmC and the down-regulation of TET1-3, TDG and IDH2 were found in GCs. The loss of 5-hmC in GCs was mainly correlated with the down-regulation of TET1.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
stomach cancer disease_progressionIEP 149735841protein:decreased expression:stomach (human)RGD 
stomach cancer disease_progressionISOIDH2 (Homo sapiens)149735841; 149735841protein:decreased expression:stomach (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Idh2  (isocitrate dehydrogenase (NADP(+)) 2)

Genes (Mus musculus)
Idh2  (isocitrate dehydrogenase 2 (NADP+), mitochondrial)

Genes (Homo sapiens)
IDH2  (isocitrate dehydrogenase (NADP(+)) 2)


Additional Information