CpG island methylation in aberrant crypt foci and cancers from the same patients.
Aberrant methylation of CpG islands is a common alteration in human colon cancer. Methylation of only a limited number of loci has been studied in aberrant crypt foci (ACF), the earliest identified premalignant lesions in the colon, and in only a limited number of lesions from the same patients. Methylation-specific PCR was used to analyze 35 ACF, samples of normal crypts with the same number of crypts as were in each ACF and 22 cancers from the same patients. Aberrant methylation in cellular retinol-binding protein 1 (CRBP1), MINT31 or H-cadherin (CDH13) was identified in 19 of 35 (54%) ACF. Hypermethylation of CRBP1, MINT31 or CDH13 was more frequent (15 of 22, 68%) in cancers. DNA methylation of CRBP1, MINT31 or CDH13 was not correlated between cancers and ACF from the same patients. Aberrant methylation was not correlated with patient age, number of crypts in the ACF or cancer stage. These results suggest that hypermethylation in the promoter region of some genes is an independent event, occurs early in human colon tumorigenesis and may play an important role during the transformation and progression of some lesions to colon cancers.
Luo
Liping
L
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Chen
Wei-dong
WD
Pretlow
Theresa P
TP
D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000235:genetics / Q000378:metabolism; D054840:Retinol-Binding Proteins, Cellular
C117536:APBA3 protein, human; D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D002352:Carrier Proteins; C099972:H-cadherin; D011506:Proteins; C518456:RBP1 protein, human; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular