title: Lymphomagenesis in Emu-myc transgenic mice does not require transgene rearrangement or mutation of myc exon 1.
abstract: In most human Burkitt's lymphomas, translocation of the myc oncogene to an immunoglobulin locus is associated with loss of myc exon 1 or with mutations near its 3' border, a region where myc transcription is attenuated and translation of a larger myc polypeptide initiates. Emu-myc transgenic mice, which bear the three myc exons coupled to an immunoglobulin enhancer, provide a model for the development of such lymphomas, because their lymphomagenesis appears to require events other than expression of the transgene. To determine whether myc rearrangement or exon 1 mutation is a necessary tumorigenic event, we examined the transgene structure and myc exon 1 sequences in Emu-myc B lymphoid tumours. Southern blots revealed no transgene rearrangements in 20 of the lymphomas, and only two tumours showed amplification (2 to 5-fold). To search for exon 1 alterations, the exon 1 mRNA region was amplified from five tumours by polymerase chain reaction and sequenced, but no mutations were found. Hence, neither excision nor mutation of exon 1 is necessary to render myc tumorigenic. The sequence analysis across the exon 1-exon 2 boundary unexpectedly revealed an ambiguity in myc splicing that predicts a variant form of the larger myc polypeptide lacking a single amino acid residue.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Post Office Royal Melbourne Hospital, Victoria, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Webb
authors.forename: G
authors.initials: G
authors.lastname: Barri
authors.forename: S
authors.initials: S
authors.lastname: Cory
authors.forename: J M
authors.initials: JM
authors.lastname: Adams
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D005091:Exons; D008223:Lymphoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D016274:Oncogene Protein p55(v-myc); D009857:Oncogenes; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D016274:Oncogene Protein p55(v-myc); D012333:RNA, Messenger; D015682:Retroviridae Proteins, Oncogenic; D004247:DNA