Intrachromosomal rearrangements fusing L-myc and rlf in small-cell lung cancer.
Chromosomal abnormalities affecting proto-oncogenes are frequently detected in human cancer. Oncogenes of the myc family are activated in several types of tumors as a result of gene amplification or chromosomal translocation. We have recently found the L-myc gene involved in a gene fusion in small-cell lung cancer (SCLC). This results in a chimeric protein with amino-terminal sequences from a novel gene named rif joined to L-myc. Here we present a preliminary structural characterization of the rlf-L-myc fusion gene, which has been found only in cells with an amplified L-myc gene. In addition, we have used somatic cell hybrids to assign the normal rlf locus to the same chromosome (chromosome 1) on which L-myc resides. Finally, we have been able to establish a physical linkage between rif and L-myc with pulsed-field gel electrophoresis. Our results demonstrate that normal rlf and L-myc genes are separated by less than 800 kb of DNA. Thus, the rlf-L-myc gene fusions are due to similar but not identical intrachromosomal rearrangements at 1p32. The presence of independent genetic lesions that cause the formation of identical chimeric rlf-L-myc proteins suggests a role for the fusion protein in the development of these tumors.
Mäkelä
T P
TP
Department of Virology, University of Helsinki, Finland.
Kere
J
J
Winqvist
R
R
Alitalo
K
K
D000818:Animals; D015139:Blotting, Southern; D018288:Carcinoma, Small Cell / Q000235:genetics*; D002460:Cell Line; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D003001:Cloning, Molecular; D006224:Cricetinae; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D015321:Gene Rearrangement; D016259:Genes, myc; D008040:Genetic Linkage; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology; D007438:Introns; D008175:Lung Neoplasms / Q000235:genetics*; D008647:Mesocricetus; D051379:Mice; D009693:Nucleic Acid Hybridization; D011519:Proto-Oncogenes; D015183:Restriction Mapping
D015342:DNA Probes; D004273:DNA, Neoplasm