Fused transcripts of c-myc and a new cellular locus, hcr in a primary liver tumor.

The proto-oncogene c-myc has been implicated in the formation of primary liver tumors in hepatitis virus-infected woodchucks. In one of these tumors, a DNA rearrangement placed the truncated c-myc gene downstream of a cellular sequence (hcr) in a head-to-tail configuration resulting in 50-fold enhanced levels of c-myc transcripts. Analysis of the tumor-specific c-myc RNA now demonstrates that transformed liver cells produce fused hcr/myc transcripts initiated from the hcr promoter and extending into c-myc coding sequences by differential splicing mechanisms. In phase fusion of the reading frames of both genes might result in the translation of the hcr/myc 2.0 kb RNA into a hybrid protein that would differ from the normal woodchuck c-myc gene product by 22 additional hcr amino acids at its amino-terminus. The production of inappropriate levels of modified or normal myc-encoded proteins is probably involved in the malignant process.