FUSION OF CHOP TO A NOVEL RNA-BINDING PROTEIN IN HUMAN MYXOID LIPOSARCOMA

HUMAN myxoid liposarcomas contain a characteristic chromosomal translo cation, t(12;16)(q13;p11)1,2, that is associated with a structural rea rrangement of the gene encoding CHOP 3, a growth arrest and DNA-damage inducible member of the C/EBP family of transcription factors4,5 resi ding on 12q13.1 6. Using a CHOP-specific complementary probe and antis erum we report here the presence of an abnormal CHOP transcript and pr otein in these tumours. Cloning of the translocation-associated CHOP g ene product revealed a fusion between CHOP and a gene provisionally na med TLS (translocated in liposarcoma). TLS is a novel nuclear RNA-bind ing protein with extensive sequence similarity to EWS7, the product of a gene commonly translocated in Ewing's sarcoma. In TLS-CHOP the RNA- binding domain of TLS is replaced by the DNA-binding and leucine zippe r dimerization domain of CHOP. Targeting of a conserved effector domai n of RNA-binding proteins to DNA may play a role in tumour formation.