HYPERVARIABLE ALLELIC EXPRESSION PATTERNS OF THE IMPRINTED IGF2 GENE IN TUMOR-CELLS

The IGF2 gene, which encodes a growth factor, is subject to genomic im printing, The frequently observed loss of IGF2 imprinting in a variety of tumors has been suggested to contribute to neoplasia, Since these reports have not documented the imprinting status of IGF2 at the cellu lar level, it cannot be excluded that the imprinting status might vary within the tumor, The possibility that loss of IGF2 imprinting in neo plastic cells reflects random imprinting patterns, was therefore addre ssed, We show here that individual cell populations of the JEG-3 chori ocarcinoma cell line display heterogenous imprinting patterns of both IGF2 and H19, In addition, a lack of correlation between IGF2 and H19 imprinting status suggests that any regional parental imprint has been functionally lost, This notion is reinforced by the observation that JEG-3 cell subclones display a range of promoter-specific IGF2 allele usage, Moreover, we observed that the imprinting status of H19 and IGF 2 were differentially modulated in JEG-3-derived tumors generated in n ude mice, The results suggest that allele-specific expression of IGF2 operates in the absence of a parental imprint, Finally, our observatio ns urge caution with respect to the general interpretation of bialleli c expression as 'loss of imprinting'.