Loss of imprinting of the insulin-like growth factor II gene occurs by biallelic methylation in a core region of H19-associated CTCF-binding sites in colorectal cancer.
We hypothesize that loss of imprinting (LOI) of the insulin-like growth factor II (IGF2) gene is associated with a predisposition to sporadic colorectal cancer. We confirmed a previously known strong correlation between LOI and microsatellite instability and showed that LOI was not a consequence of microsatellite instability or mismatch repair deficiency. LOI of IGF2 correlated strongly with biallelic hypermethylation of a core of five CpG sites in the insulator region of IGF2/H19, which is a known CTCF-binding element. As this methylation-dependent LOI was present in both tumors and normal colonic mucosa, it is possible that hypermethylation creates a field defect predisposing to cancer.
Nakagawa
H
H
Division of Human Cancer Genetics, Comprehensive Cancer Center, Ohio State University, 420 West 12th Avenue, Columbus, OH 43210, USA.
Chadwick
R B
RB
Peltomaki
P
P
Plass
C
C
Nakamura
Y
Y
de La Chapelle
A
A
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics*; D000483:Alleles; D000818:Animals; D020137:Base Pair Mismatch / Q000235:genetics; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002352:Carrier Proteins; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D018899:CpG Islands; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000502:physiology; D019175:DNA Methylation; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020868:Gene Silencing; D005809:Genes, Regulator; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D018392:Genomic Imprinting; D006579:Heterozygote; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051379:Mice; D018895:Microsatellite Repeats; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D010641:Phenotype; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D012097:Repressor Proteins; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002352:Carrier Proteins; C000619698:Ctcf protein, mouse; D004268:DNA-Binding Proteins; C094335:H19 long non-coding RNA; C501486:MLH1 protein, human; C501485:Mlh1 protein, mouse; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; D014157:Transcription Factors; D007335:Insulin-Like Growth Factor II; D004248:DNA (Cytosine-5-)-Methyltransferases; D000070957:MutL Protein Homolog 1