Correlation of DNA hypomethylation at pericentromeric heterochromatin regions of chromosomes 16 and 1 with histological features and chromosomal abnormalities of human breast carcinomas.
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.
Tsuda
Hitoshi
H
Pathology Division, National Cancer Center Research Institute and Hospital, Tokyo, Japan. htsuda@cc.ndmc.ac.jp
Takarabe
Teruko
T
Kanai
Yae
Y
Fukutomi
Takashi
T
Hirohashi
Setsuo
S
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1; D002885:Chromosomes, Human, Pair 16; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D006570:Heterochromatin / Q000235:genetics* / Q000378:metabolism; D006801:Humans
D004273:DNA, Neoplasm; D006570:Heterochromatin