Rearrangement of the oncogene c-mos in mouse myeloma NSI and hybridomas.
The activity and products of cellular oncogenes can be altered by various processes, such as the nearby integration of a retroviral genome, point mutation within the oncogene coding region, gene amplification, and chromosomal translocation (reviewed in ref. 1). Our work has provided an example of oncogene activation by yet a different process; the integration of an endogenous retrovirus-like DNA element (identified as an intracisternal A particle or IAP genome) within the coding region of the oncogene c-mos in a mouse plasmacytoma, XRPC 24. The rearranged c-mos gene of XRPC24 is actively transcribed and has transforming activity, suggesting some role for activated c-mos in the progression of the XRPC24 tumour. In this report we describe rearrangement of c-mos in a second mouse plasmacytoma, NSI, and in two hybridomas. In this case, as in XRPC24, c-mos was split by the insertion of a IAP genome. The rearranged c-mos genes (rc-mos) of NSI and XRPC24 differ in three major aspects: (1) The site of IAP integration in c-mos is in codon 30 in NSI but in codon 88 in XRPC24; (2) The orientation of the integrated IAP relative to c-mos is 'tail-to-head' in NSI and 'head-to-head' in XRPC24; and (3) transcriptional activity of rc-mos in NSI is much lower than in XRPC24. The two latter points suggest a correlation between the orientation of the long terminal repeat (LTR) of IAP relative to c-mos and its activity upon IAP integration.
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation; D006825:Hybridomas / Q000502:physiology*; D051379:Mice; D009857:Oncogenes; D010954:Plasmacytoma / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic