TY - JOUR
T1 - Transposition and amplification of oncogene-related sequences in human neuroblastomas
AU - Kohl, Nancy E.
AU - Kanda, Naotoshi
AU - Schreck, Rhona R.
AU - Bruns, Gail
AU - Latt, Samuel A.
AU - Gilbert, Fred
AU - Alt, Frederick W.
N1 - Funding Information:
We are grateful to Drs. D. Ishii, John Mills, and Warren Nichols for providrng cell lines, to P. L. Weldy for assistance with the zonal centrifugation, to Drs. 0. J. and D. A. Miller for help with the caryotypic analyses, to Dr. J. Ravetch for provrding the human JH probe, and to Drs. L. Pirada, R. Weinberg, D. Liebowrtz, A. Bank, R. Taub, and P. Leder for providing various oncogene probes. We would also like to thank Drs. R. Axel, S. Goff, and G. Yancopoulos for critically reading thus manuscript. This work was supported by Amerrcan Cancer Society grants NP-393 and CD-36 (to F. W. A. and S. A. L.) and NIH grant HD-18658 (to S. A. L.). N. K. was a Fogarty fnter-national Fellow. F. W. A. is the recipient of an lmra T. Hirsch1 Career Scientist Award.
PY - 1983/12
Y1 - 1983/12
N2 - We have cloned a 2.0-kb EcoRI fragment of human genomic DNA (NB-19-21) which has homology to the v-myc oncogene but is distinct from the classical c-myc gene. This sequence is amplified from 25- to 700-fold in eight of nine tested human neuroblastoma cell lines which contain either homogeneously staining regions or double minutes (HSRs or DMs), the caryological manifestations of amplified genes. In the remaining line, the c-myc proto-oncogene is amplified approximately 30-fold. NB-19-21 hybridizes to a 3.2-kb cytoplasmic, poly(A)+ RNA species that is abundant only in lines in which the sequence is amplified. We propose that the gene encoding the NB-19-21-related RNA species may represent a new oncogene, which we call N-myc. NB-19-21 derives from chromosome 2; but in the five HSR-containing lines that have amplified this sequence, none has HSRs on chromosome 2. NB-19-21 is associated with DMs in a DM-containing line. A second, randomly cloned, amplified DNA segment from the HSR of one of the neuroblastoma lines is amplified in a subset of the lines in which NB-19-21 is amplified. In addition, this probe identifies a novel joint in the amplification unit of one line relative to that of the others. We suggest that, in the eight lines which have amplified NB-19-21, the amplification units are overlapping, but not identical, and that transposition of the common sequences may occur prior to amplification.
AB - We have cloned a 2.0-kb EcoRI fragment of human genomic DNA (NB-19-21) which has homology to the v-myc oncogene but is distinct from the classical c-myc gene. This sequence is amplified from 25- to 700-fold in eight of nine tested human neuroblastoma cell lines which contain either homogeneously staining regions or double minutes (HSRs or DMs), the caryological manifestations of amplified genes. In the remaining line, the c-myc proto-oncogene is amplified approximately 30-fold. NB-19-21 hybridizes to a 3.2-kb cytoplasmic, poly(A)+ RNA species that is abundant only in lines in which the sequence is amplified. We propose that the gene encoding the NB-19-21-related RNA species may represent a new oncogene, which we call N-myc. NB-19-21 derives from chromosome 2; but in the five HSR-containing lines that have amplified this sequence, none has HSRs on chromosome 2. NB-19-21 is associated with DMs in a DM-containing line. A second, randomly cloned, amplified DNA segment from the HSR of one of the neuroblastoma lines is amplified in a subset of the lines in which NB-19-21 is amplified. In addition, this probe identifies a novel joint in the amplification unit of one line relative to that of the others. We suggest that, in the eight lines which have amplified NB-19-21, the amplification units are overlapping, but not identical, and that transposition of the common sequences may occur prior to amplification.
UR - https://www.scopus.com/pages/publications/0021047844
U2 - 10.1016/0092-8674(83)90169-1
DO - 10.1016/0092-8674(83)90169-1
M3 - Article
C2 - 6197179
AN - SCOPUS:0021047844
SN - 0092-8674
VL - 35
SP - 359
EP - 367
JO - Cell
JF - Cell
IS - 2 PART 1
ER -