Changes in DNA methylation status are not only important for regulating gene expression but are also suggested to induce
chromosome instability. To reveal the correlation of DNA methylation status in
heterochromatin regions with
tumor histology and with chromosome alterations, DNA methylation status was examined by Southern blot analysis, and numerical and structural chromosome alterations, including the formation of der(16)t(1;16)/der(1;16), were examined by fluorescence in situ hybridization at the two loci in the pericentromeric satellite 2 regions of chromosomes 16 and 1 in 39 human
breast carcinomas.
DNA hypomethylation at the D16Z3 and the D1Z1 loci was detected in 31% (12 of 39) and 36% (12 of 33) of
carcinomas, respectively, and mostly concurred.
DNA hypomethylation was more frequent in the
carcinoma group of more aggressive histological types or grade 3 than in the
carcinoma of less aggressive histological types or grades 1 and 2, and tended to be more frequent in
carcinomas with > or =4 copies of chromosomes 16 and/or 1 than in
carcinomas with < or =3 copies of any of these chromosomes. The frequency of
DNA hypomethylation at the D16Z3 and the D1Z1 loci was 45% (10 of 22) and 53% (9 of 17) in
carcinomas without der(16)t(1;16)/der(1;16), formation, but only 12% (2 of 17) and 19% (3 of 16) in
carcinoma with der(16)t(1;16)/der(1;16), respectively (P = 0.036 and 0.070). The 16q breakage was almost equally detected between
carcinoma groups with and without the
DNA hypomethylation.
DNA hypomethylation in the satellite 2 regions was suggested to be associated with the accumulation of a large number of numerical chromosome alterations and involved in the development of
breast carcinomas of aggressive histological features. On the contrary,
chromosome instability induced by mechanisms other than
DNA hypomethylation in
heterochromatin regions might cause the formation of der(16)t(1;16)/der(1;16) and less aggressive
breast carcinomas.