Human small-cell lung cancers show amplification and expression of the N-myc gene.
We have found that 6 of 31 independently derived human small-cell lung cancer (SCLC) cell lines have 5- to 170-fold amplified N-myc gene sequences. The amplification is seen with probes from two separate exons of N-myc, which are homologous to either the second or the third exon of the c-myc gene. Amplified N-myc sequences were found in a tumor cell line started prior to chemotherapy, in SCLC tumor samples harvested directly from tumor metastases at autopsy, and from a resected primary lung cancer. Several N-myc-amplified tumor cell lines also exhibited N-myc hybridizing fragments not in the germ-line position. In one patient's tumor, an additional amplified N-myc DNA fragment was observed and this fragment was heterogenously distributed in liver metastases. In contrast to SCLC with neuroendocrine properties, no non-small-cell lung cancer lines examined were found to have N-myc amplification. Fragments encoding two N-myc exons also detect increased amounts of a 3.1-kilobase N-myc mRNA in N-myc-amplified SCLC lines and in one cell line that does not show N-myc gene amplification. Both DNA and RNA hybridization experiments show that in any one SCLC cell line, only one myc-related gene is amplified and expressed. We conclude that N-myc amplification is both common and potentially significant in the tumorigenesis or tumor progression of SCLC.
Nau
M M
MM
Brooks
B J
BJ
Carney
D N
DN
Gazdar
A F
AF
Battey
J F
JF
Sausville
E A
EA
Minna
J D
JD
D018288:Carcinoma, Small Cell / Q000235:genetics*; D002460:Cell Line; D004273:DNA, Neoplasm / Q000032:analysis; D005784:Gene Amplification; D005786:Gene Expression Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D011061:Poly A / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D012689:Sequence Homology, Nucleic Acid
D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011061:Poly A