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© 1994 Oxford University Press

OTHER

Mono- and bi-allelic expression of insulin-like growth factor II gene in human muscle tumors

Paolo V. Pedone, Roberto Tirabosco1, Andrea O. Cavazzana1,3, Paola Ungaro, Giuseppe Basso2,3, Roberto Luksch4, Modesto Carli2, Carmelo B. Bruni, Rodolfo Frunzio5 and Andrea Riccio*

Centro di Endocrinologia ed Oncologia Spenmentale, CNR, Dipartimento di Biologia e Pataologia Cellulare e Molecolare Torvergata, Italy 1Istituto di Anatomia Patologica, Università di Roma Torvergata, Italy 2II Clinica Pediatrica, Università di Padova FONOP, Milano, Italy 3Gruppo Biologico Oncologia Tumori Solidi Pediatrici FONOP, Milano, Italy 4Istituto Nazionale dei Tumori Milano, Italy 5Dipartimento di Chimica Organica e Biologica, Università di Napoli ‘Federico II’ Torvergata, Italy

*To whom correspondence should be addressed at: Centro di Endocrinologia ed Oncologia Sperimentale, CNR, Università di Napoli, via Pansini 5, 80131 Napies, Italy

Received March 14, 1994; Revised May 4, 1994; Accepted May 4, 1994

Insulin-like growth factor II (IGF-II) is a mitogen for many cell types 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 inherited from the father is active and the allele inherited from the mother is inactive in most normal tissues. IGF-II expression is activated in several types of human neoplasms and an alteration of IGF-II imprinting has been described in Beckwith–Wiedemann syndrome and Wilms' tumour. Here we show that monoallelic expression of IGF-II gene is conserved in normal adult muscle tissue whereas two or more copies of active IGF-II alleles, arising by either relaxation of imprinting or duplication of the active allele, are found in 9 out of 11 (82%) rhabdomyo-sarcomas retaining heterozygosity at 11p15, regardless of the histological subtype. Since IGF-II has been indicated as an autocrine growth factor for rhabdomyosarcoma cells, these findings strongly suggest that acquisition of a double dosage of active IGF-II gene is an important step for the initiation or progression of rhabdomyosarcoma tumorigenesis. Among different types of muscle tumors, relaxation of imprinting seems to arise prevalently in rhabdomyosarcomas, since we have detected only one case of partial reactivation of the maternal IGF-II allele out of 7 lelomyosarcomas tested.


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