Interacisternal A-particle (IAP) genes show similar patterns of hypomethylation in established and primary mouse...

Alterations in cell programming associated with neoplastic transformation may involve widespread changes in patterns of DNA methylation. Increased expression of IAP elements in plasmacytomas compared with LPS-stimulated normal B-cells is accompanied by extensive hypomethylation of IAP sequences (Mietz and Kuff 1990), subsets of which are revealed with the LS2, LS3 and T1 probes. Multiple common LS- and PC-specific IAP loci are hypomethylated in established plasmacytomas, showing that hypomethylation does not occur entirely randomly. Many of the same IAP loci are hypomethylated in primary plasmacytomas induced by two different methods, as soon as recognizable tumor tissue can be isolated. In primary tumors hypomethylation frequently appears to occur in DNA flanking the IAP elements. In the established tumors the hypomethylated sites occur primarily in the IAP LTR, suggesting that for these loci hypomethylation begins in the flanking DNA and is extended into the IAP LTRs during progression of the tumors. The newly hypomethylated IAP LTRs in primary plasmacytomas (as compared to normal B cells) may provide a set of reporter genes for chromosomal regions that are characteristically hypomethylated in these transformed cells and that may contain cellular genes whose activation is related to the transformation process.