HUMAN BREAST AND COLON CANCERS EXHIBIT ALTERATIONS OF DNA METHYLATIONPATTERNS AT SEVERAL DNA SEGMENTS ON CHROMOSOMES 11P AND 17P

In breast and colon adenocarcinomas methylation patterns at CCGC sites of several loci located on the short arm of chromosome 11 were determ ined by Southern blot analysis. Results obtained indicate that all tum or samples (20/20) exhibit DNA methylation changes when compared to th eir normal counterparts. In colon tumors, gamma-globin gene is usually hypomethylated (9/10), whereas Ha-ras gene, which is located in the s ame region, retains an unmodified DNA methylation pattern. Hypomethyla tion of parathyroid hormone (5/10) and catalase genes (4/10) are also frequently detected in colon tumor specimens. For the catalase gene th e region around exon 2 is the only one which is affected by these chan ges. In breast adenocarcinoma, modifications of the methylation patter ns 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 ste p in breast tumorigenesis. In addition, hypermethylation of a CpG isla nd is also observed at the locus 17p13.3 in both colon (5/5) and breas t (4/9) adenocarcinomas. In the tumoral tissues analyzed these hyperme thylations are not associated with the hypermethylation of the 5' flan king sequences which contain a limited amount of CpG. Some of these al terations seem, therefore, to be tumor and sequence specific. (C) 1994 Wiley-Liss, Inc.