Loss of imprinting of IGF2 in fibroadenomas and phyllodes tumors of the breast

Abstract

Loss of imprinting (LOI) of insulin-like growth factor 2 (IGF2) is thought to be implicated in the pathogenesis of some tumors by upregulating IGF2 mRNA but its role in the pathogenesis of fibroadenomas (FAs) and phyllodes tumors (PTs) of the breast is yet to be studied. LOI of IGF2 was investigated in 25 FAs and 17 PTs which were heterozygous for Apa I polymorphism, and was found to be present in 13 FAs and 12 PTs. IGF2 mRNA expression was more upregulated in FAs and PTs than in paired surrounding normal tissues and laser microdissection showed that IGF2 mRNA expression was significantly higher in the stromal than the epithelial cells. LOI was not associated with upregulation of IGF2 mRNA, nor were MED12 mutations and methylation status of the differentially methylated region 0 (DMR0) of IGF2. These results demonstrate that IGF2 mRNA expression is more upregulated in FAs and PTs than in normal tissues, especially in their stromal cells, but such an upregulation is not related to LOI of IGF2, and that hypomethylation of DMR0 is unlikely to be involved in induction of LOI.