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.
Katrincsakova
Beata
B
Center for Human Genetics, Catholic University Leuven, Leuven, Belgium.
Takeda
Haruko
H
Urbankova
Helena
H
Michaux
Lucienne
L
Jarosova
Marie
M
Vandenberghe
Peter
P
Georges
Michel
M
Charlier
Carole
C
Wlodarska
Iwona
I
D000483:Alleles; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D002883:Chromosomes, Human, Pair 14; D005260:Female; D050438:Genes, Immunoglobulin Heavy Chain; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D015448:Leukemia, B-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016393:Lymphoma, B-Cell / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D010290:Parents; D011506:Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding
D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C498907:MEG3 non-coding RNA, human; D008565:Membrane Proteins; D011506:Proteins; D062085:RNA, Long Noncoding