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 tumo r-predisposing overgrowth disorders, such as Beckwith-Wiedemann syndrome. I n a previous study, the authors revealed that certain patients with childho od acute leukemia and neuroblastoma had had rapid somatic growth after birt h, 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 c ontrol individuals was amplified by polymerase chain reaction (PCR). Patien ts who had heterozygous genotype were selected as informative cases using A pa 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, a nd direct sequence was performed for determining allele specific transcript ion. RESULTS. Twenty of 22 infant leukemia blasts and ail of 16 neuroblastoma ce lls showed normal monoallelic expression of IGF-2 as well as 23 controls. T he 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 main tained in childhood neuroblastoma. The results suggest that LOI of IGF-2 do es not play a major role in the carcinogenesis of these diseases or in rapi d physical growth of the patients. Cancer 2000;88:2372-7. (C) 2000 American Cancer Society.