Imprinting status of DLK1 gene in brain tumors and lymphomas.
DLK1 and GTL2 are reciprocally imprinted genes on human chromosome 14q32. DLK1 encodes a transmembrane protein that is a paternally expressed gene. The maternally expressed GTL2 allele encodes a non-translated RNA. Many of features of DLK1/GTL2 are remarkably similar to those of the prototypical IGF2/H19 reciprocally imprinted gene pair. Imprinting status of IGF2 has been studied in many types of tumors, and loss of imprinting (LOI) leads to biallelic expression of IGF2 in most of these tumors. The imprinting status of DLK1 has seldom been investigated in clinical tumor samples. We examined whether DLK1 was imprinted in brain tumors and lymphomas by analyzing a single nucleotide polymorphism (SNP), rs1802710. Analysis of 47 brain tumors and 55 lymphomas found that 23 and 29 of them were heterozygous for rs1802710, respectively. Monoallelic expression of DLK1 was detected in the heterozygous samples. These data show that imprinting of DLK1 is maintained in brain tumors and lymphomas, even though the DLK1 gene is very analogous to the IGF2 gene in its DNA structure and regulation. Also, the high frequency of heterozygosity (about 50%) showed that the polymorphic site that we chose is a good genomic marker for imprinting studies of the DLK1 gene in additional tumor types.
Yin
Dong
D
Division of Hematology and Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA 90048, USA. dong.yin@cshs.org
Xie
Dong
D
De Vos
Sven
S
Liu
Gentao
G
Miller
Carl W
CW
Black
Keith L
KL
Koeffler
H Phillip
HP
D000483:Alleles; D001932:Brain Neoplasms / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004815:Epidermal Growth Factor / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D019656:Loss of Heterozygosity; D008223:Lymphoma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational
D004273:DNA, Neoplasm; D006023:Glycoproteins; D004815:Epidermal Growth Factor