Hypomethylation of L1 retrotransposons in colorectal cancer and adjacent normal tissue.
OBJECTIVE
Malignant cells often exhibit perturbations in the pattern of cytosine methylation. Hypermethylation of CpG islands has been extensively documented, but genome-wide hypomethylation is also a common feature of malignant cells. The bulk of cytosine methylation in the mammalian genome occurs on repetitive elements. This study analysed the methylation status of L1 retrotransposons in colorectal cancer.


METHODS
Methylation-sensitive Southern blotting was used to determine L1 promoter methylation in colon tumours, adjacent normal tissue, and normal colonic mucosa from healthy individuals.


RESULTS
Hypomethylation of L1 promoter sequences was detected in all tumours but was also detected in the histologically normal colonic mucosa of 6 of 19 cancer patients, even at a considerable distance from the tumour. L1 hypomethylation was not detected in matched normal peripheral blood, lymph node or smooth muscle tissue from cancer patients or in the colonic mucosa of 14 healthy individuals. We also assayed for the total proportion of methylated CpG in normal bowel specimens from normal and colon cancer patients. Normal mucosa from cancer patients exhibited lower levels of genomic methylation than the mucosa from healthy individuals, and levels were significantly lower in those patients exhibiting L1 promoter hypomethylation.


CONCLUSIONS
These results suggest that genomic hypomethylation is an early event in tumourigenesis. Progressive demethylation of L1 promoter sequences could lead to disturbance of normal gene expression and facilitate the process of neoplastic progression.
Suter
Catherine M
CM
Medical Oncology Department, St. Vincent's Hospital, Darlinghurst, 2010 Sydney, Australia.
Martin
David I
DI
Ward
Robyn L
RL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins