title: Human small-cell lung cancers show amplification and expression of the N-myc gene.
abstract: 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.
authors.forename: M M
authors.initials: MM
authors.lastname: Nau
authors.forename: B J
authors.initials: BJ
authors.lastname: Brooks
authors.forename: D N
authors.initials: DN
authors.lastname: Carney
authors.forename: A F
authors.initials: AF
authors.lastname: Gazdar
authors.forename: J F
authors.initials: JF
authors.lastname: Battey
authors.forename: E A
authors.initials: EA
authors.lastname: Sausville
authors.forename: J D
authors.initials: JD
authors.lastname: Minna
mesh_terms: 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
chemical_list: D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011061:Poly A