SATR-1 hypomethylation is a common and early event in breast cancer.
Genome stability and normal gene expression are maintained by a fixed and predetermined DNA methylation pattern, which becomes abnormal in malignant cells. Hypomethylation of satellite DNA sequences is frequently found in tumors and has been associated with an increased frequency of DNA rearrangements and chromosome instability. In this work, we used methylation-sensitive arbitrarily primed polymerase chain reaction (MSAP-PCR) to identify differentially methylated DNA fragments in normal and tumor breast samples. We identified a novel differentially methylated fragment located on chromosome 5 with high similarity to a SATR-1 satellite sequence. This fragment was found to be hypomethylated in 63% of breast tumor cell lines and in 86% of breast tumors relative to normal breast tissue. We found that normal tissue adjacent to breast tumors displayed a variable decrease in methylation and that the decrease observed for most of these adjacent samples was higher than observed for normal breast tissue derived from reduction mammoplasty. The methylation decrease was, however, significantly higher in tumor samples than in adjacent tissue (chi2= 154, 1 df, P < 10(-4)), suggesting that SATR-1 hypomethylation frequently occurs in the early stages of tumor development. Our results highlight the importance of global DNA hypomethylation as a contributing factor in breast tumorigenesis.
Costa
Fabrício F
FF
Laboratory of Molecular Biology and Genomics, Ludwig Institute for Cancer Research, Rua Prof. Antonio Prudente, 109, 4th floor, 01509-010 São Paulo, SP Brazil.
Paixão
Valeria A
VA
Cavalher
Felicia P
FP
Ribeiro
Karina B
KB
Cunha
Isabela W
IW
Rinck
José Augusto
JA
O'Hare
Michael
M
Mackay
Alan
A
Soares
Fernando A
FA
Brentani
Ricardo R
RR
Camargo
Anamaria A
AA
D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D017931:DNA Primers; D005260:Female; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D016133:Polymerase Chain Reaction
D017931:DNA Primers