Complex intrachromosomal rearrangement in the process of amplification of the L-myc gene in small-cell lung cancer.
The L-myc gene was first isolated from a human small-cell lung cancer (SCLC) cell line on the basis of its amplification and sequence similarity to c-myc and N-myc. A new mechanism of L-myc activation which results from the production of rlf-L-myc fusion protein was recently reported. On the basis of our earlier observation of a rearrangement involving amplified L-myc in an SCLC cell line, ACC-LC-49, we decided to investigate this rearrangement in detail along with the structure of L-myc amplification units in five additional SCLC cell lines. We report here the identification of a novel genomic region, termed jal, which is distinct from rlf and is juxtaposed to and amplified with L-myc during the process of DNA amplification of the region encompassing L-myc. Long-range analysis using pulsed-field gel electrophoresis revealed that the amplified L-myc locus is involved in highly complex intrachromosomal rearrangements with jal and/or rlf. Our results also suggest that the simultaneous presence of rearrangements both in rlf intron 1 and in regions immediately upstream of L-myc may be necessary for the expression of rlf-L-myc chimeric transcripts.
Sekido
Y
Y
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Takahashi
T
T
Mäkelä
T P
TP
Obata
Y
Y
Ueda
R
R
Hida
T
T
Hibi
K
K
Shimokata
K
K
Alitalo
K
K
Takahashi
T
T
D018288:Carcinoma, Small Cell / Q000235:genetics*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D016521:Electrophoresis, Gel, Pulsed-Field; D005784:Gene Amplification; D015870:Gene Expression; D015321:Gene Rearrangement; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic
D012333:RNA, Messenger