Methylation Analysis Of The Imprinted Dlk1-Gtl2 Domain Supports The Random Parental Origin Of The Igh-Involving Del(14q) In B-Cell Malignancies

Leukemias/lymphomas with IGH-involving del(14q)(1) commonly lose the DLK1-GTL2 imprinted domain that comprises several paternally and maternally expressed genes, including a cluster of microRNAs. Given that deletion of this region could lead to inactivation of a monoallelically expressed tumor suppressor gene, our study aimed at determination of the parental origin of del(14q/IGH). The designed allele-specific methylation study of the DLK1/GTL2 intergenic differentially methylated region allowed us to determine the parental origin of del(14q/IGH) in 9/20 analyzed cases. In six cases del(14q/IGH) was of the paternal origin and in three cases of the maternal origin. These findings argue against the concept that a TSG/anti-oncomir located in the imprinted region is systematically inactivated by a targeted deletion of its functional allele.