MONO-ALLLIC AND BI-ALLELIC EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR-II GENE IN HUMAN MUSCLE TUMORS

Insulin-like growth factor II (IGF-II) is a mitogen for many cell type s and an important modulator of muscle growth and differentiation. IGF -II gene is prevalently expressed during prenatal development and its gene activity is regulated by genomic imprinting, in that the allele i nherited from the father is active and the allele inherited from the m other is inactive in most normal tissues. IGF-II expression is activat ed in several types of human neoplasms and an alteration of IGF-II imp rinting has been described in Beckwith-Wiedemann syndrome and Wilms' t umor. Here we show that monoallelic expression of IGF-II gene is conse rved in normal adult muscle tissue whereas two or more copies of activ e IGF-II alleles, arising by either relaxation of imprinting or duplic ation of the active allele, are found in 9 out of 11 (82%) rhabdomyosa rcomas retaining heterozygosity at 11p15, regardless of the histologic al subtype. Since IGF-II has been indicated as an autocrine growth fac tor for rhabdomyosarcoma cells, these findings strongly suggest that a cquisition of a double dosage of active IGF-II gene is an important st ep for the initiation or progression of rhabdomyosarcoma tumorigenesis . Among different types of muscle tumors, relaxation of imprinting see ms to arise prevalently in rhabdomyosarcomas, since we have detected o nly one case of partial reactivation of the maternal IGF-II allele out of 7 leiomyosarcomas tested.