Transcriptional activation of the translocated c- myc oncogene in Burkitt lymphoma

Abstract

Translocations of VH genes from chromosome 14 to chromosome 8 and of the c-myconcogene from chromosome 8 to chromosome 14 occur in Burkitt lymphomas with the t(8;14) chromosome translocation. An association of the c-myc gene with the C.mu. Ig gene was observed in some but not all Burkitt lymphomas studied previously. The organization of the human H chain locus and of the c-myc gene was investigated in the P3HR-1 Burkitt lymphoma cell line. Because mouse/P3HR-1 somatic cell hybrids that retain only the 14q + chromosome and no other human chromosome contain the human C.mu. and C.gamma. genes but not VH genes, the breakpoint on chromosome 14 in P3HR-1 cells is distal to CUm and between C.mu. and VH. The breakpoint of human chromosome 14 differs in different Burkitt lymphoma cell lines. The human c-myc oncogene translocated to chromosome 14 in the P3HR-1 cell line is not recombined with the C.mu. gene. The breakpoint on human chromosome 8 may therefore also differ in different Burkitt lymphoma cell lines, because DNA rearrangement of the c-myc gene with the C.mu. gene was observed in only some of the Burkitt lymphoma cell lines studied elsewhere. High levels of transcripts of the c-myc oncogene were observed in Burkitt lymphomas with translocated c-myc oncogenes both rearranged and unrearranged. The translocation of a c-myc oncogene to the heavy chain locus on human chromosome 14 is apparently sufficient for its transcriptional activation and may be an essential step in the pathway leading to neoplasia.