MOLECULAR ANALYSIS OF A PATIENT WITH BECKWITH-WIEDEMANN SYNDROME, RHABDOMYOSARCOMA AND RENAL-CELL CARCINOMA

We described a patient with Beckwith-Wiedemann syndrome associated with rhabdomyosarcoma (RMS), and renal cell carcinoma (RCC). Karyotypes of peripheral lymphocytes and RMS cells were normal. DNA analyses showed maternal loss of heterozygosity (LOH) at 11p15 region in RMS but not in RCC. The insulin-like growth factor II gene (IGF2) was found to be expressed at a moderate level in RMS but not in RCC by in situ hybridization. Each of parental allele-derived IGF2 transcript was detected in RCC, while maternal allele-derived transcript was weak in RMS because of maternal LOH. These results;suggest that (1) loss of imprinting (LOT) of IGF2 might be responsible for BWS, (2) on the other hand, LOI itself might not induce tumor occurrence in tissues where the control of tissue-specific expression of IGF2 is maintained, (3) increased expression of IGF2 due to maternal loss of a putative controller gene for IGF2 at 11p15 might predispose to sustaining tumorigenic mutations and tumor progression, (4) loss of a putative once-suppressor gene at 11p15 might induce RMS occurrence. The cause of RCC was thought to be different from that of RMS.