Abstract:
:Drug-induced DNA demethylation in normal human cells and inherited localized hypomethylation in mitogen-stimulated lymphocytes from patients with a rare recessive disease (ICF: immunodeficiency, centromeric region instability, facial anomalies) are associated with karyotypic instability. This chromosomal recombination is targeted to heterochromatin in the vicinity of the centromere (pericentromeric region) of human chromosome 1. Pericentromeric rearrangements in this chromosome as well as overall genomic hypomethylation are frequently observed in many kinds of cancer, including breast adenocarcinoma. We found that almost half of 25 examined breast adenocarcinomas exhibited hypomethylation in satellite 2 DNA, which is located in the long region of heterochromatin adjacent to the centromere of chromosome 1 and is normally highly methylated. One of the 19 examined non-malignant breast tissues displaying fibrocystic changes was similarly hypomethylated in this satellite DNA. We also looked at an opposing type of methylation alteration in these cancers, namely, hypermethylation in a tumor-suppressor gene region that is frequently hypermethylated in breast cancers. We found that increased methylation in the E-cadherin promoter region and decreased methylation in satellite 2 DNA were often present in the same breast cancers. While hypermethylation in certain tumor-suppressor gene regions may favor tumorigenesis by repressing transcription, demethylation of other DNA sequences may predispose to cancer-promoting chromosomal re-arrangements.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Narayan A,Ji W,Zhang XY,Marrogi A,Graff JR,Baylin SB,Ehrlich Mdoi
10.1002/(sici)1097-0215(19980911)77:6<833::aid-ijcsubject
Has Abstractpub_date
1998-09-11 00:00:00pages
833-8issue
6eissn
0020-7136issn
1097-0215pii
10.1002/(SICI)1097-0215(19980911)77:6<833::AID-IJCjournal_volume
77pub_type
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