NORMAL AND REARRANGED PAX3 EXPRESSION IN HUMAN RHABDOMYOSARCOMA

PAX3, a member of the PAX-gene family, encodes a nuclear transcription factor that is transiently expressed in the neural tube and in muscle progenitor cells and regulates embryonal development in the mouse. To gether with the FKHR gene it is involved in the t(2;13)(q35;q14), a sp ecific translocation associated with alveolar rhabdomyosarcoma (ARMS). As a consequence of the rearrangement two chimeric transcripts origin ate: FKHR-PAX3 and PAX3-FKHR. We studied the expression of wild type P AX3 and the chimeric transcripts originating from the t(2;13) in a ser ies of 23 rhabdomyosarcomas (RMS) of childhood, by reverse transcripta se polymerase chain reaction (RT-PCR). Wild type PAX3 was detected in 48% of the RMS, whereas another 39% were positive only after nested PC R. Normal adult skeletal muscle showed a very weak expression of PAX3, but fetal muscle did not express PAX3. PAX3-FKHR was found in 11 of 1 5 alveolar RMS, 7 of which were positive also for the reciprocal trans cript, whereas no RMS expressed FKHR-PAX3 alone. These results confirm that the PAX3-FKHR transcript is specifically associated with the alv eolar RMS and that it is a more sensitive marker of the t(2;13) than t he reciprocal product FKHR-PAX3, Furthermore, the finding of PAX3 expr ession with or without PAX3-FKHR transcript in the great majority of t he cases raises the question of whether PAX3 expression could play a r ole in the pathogenesis of RMS. (C) Elsevier Science Inc., 1998.