Genomic imprinting of insulin-like growth factor-2 in infant leukemia and childhood neuroblastoma.
BACKGROUND
Loss of imprinting (LOI) of insulin-like growth factor-2 (IGF-2) has been implicated in the pathogenesis of certain human cancers and tumor-predisposing overgrowth disorders, such as Beckwith-Wiedemann syndrome. In a previous study, the authors revealed that certain patients with childhood acute leukemia and neuroblastoma had had rapid somatic growth after birth, suggesting the involvement of growth factor(s) in tumorigenesis. In the current study, the authors examined whether relaxation of IGF-2 imprinting occurred in infant leukemia and childhood neuroblastoma.


METHODS
The genomic DNA of infant leukemia, childhood neuroblastoma, and control individuals was amplified by polymerase chain reaction (PCR). Patients who had heterozygous genotype were selected as informative cases using Apa I polymorphism in exon 9 of the IGF-2 gene. Total RNA was isolated from informative cases, followed by cDNA synthesis. cDNA was amplified by PCR, and direct sequence was performed for determining allele specific transcription.


RESULTS
Twenty of 22 infant leukemia blasts and all of 16 neuroblastoma cells showed normal monoallelic expression of IGF-2 as well as 23 controls. The height and weight of two acute lymphoblastic leukemia patients with LOI were within normal ranges for Japanese children.


CONCLUSIONS
The current study revealed that the imprinting status of IGF-2 was generally maintained in infant leukemia and confirmed that it was maintained in childhood neuroblastoma. The results suggest that LOI of IGF-2 does not play a major role in the carcinogenesis of these diseases or in rapid physical growth of the patients.
Hattori
H
H
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Matsuzaki
A
A
Suminoe
A
A
Ihara
K
K
Eguchi
M
M
Tajiri
T
T
Suita
S
S
Ishii
E
E
Hara
T
T
D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D007223:Infant; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D007938:Leukemia / Q000235:genetics*; D008297:Male; D009447:Neuroblastoma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D007335:Insulin-Like Growth Factor II