Human breast and colon cancers exhibit alterations of DNA methylation patterns at several DNA segments on chromosomes...

In breast and colon adenocarcinomas methylation patterns at CCGG sites of several loci located on the short arm of chromosome 11 were determined by Southern blot analysis. Results obtained indicate that all tumor samples (20/20) exhibit DNA methylation changes when compared to their normal counterparts. In colon tumors, gamma-globin gene is usually hypomethylated (9/10), whereas Ha-ras gene, which is located in the same region, retains an unmodified DNA methylation pattern. Hypomethylation of parathyroid hormone (5/10) and catalase genes (4/10) are also frequently detected in colon tumor specimens. For the catalase gene the region around exon 2 is the only one which is affected by these changes. In breast adenocarcinoma, modifications of the methylation patterns are less frequently observed. However, hypomethylation of the gamma-globin gene is a very common event in these tumors (8/10), and it is also detected (2/2) in lobular carcinoma in situ which is an early step in breast tumorigenesis. In addition, hypermethylation of a CpG island is also observed at the locus 17p13.3 in both colon (5/5) and breast (4/9) adenocarcinomas. In the tumoral tissues analyzed these hypermethylations are not associated with the hypermethylation of the 5' flanking sequences which contain a limited amount of CpG. Some of these alterations seem, therefore, to be tumor and sequence specific.