L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer

Marion M. Nau, Burke J. Brooks, James Battey, Edward Sausville, Adi F. Gazdar, Ilan R. Kirsch, O. Wesley McBride, Virginia Bertness, Gregory F. Hollis, John D. Minna

Research output: Contribution to journalArticle

421 Scopus citations

Abstract

Altered structure and regulation of the c-myc proto-oncogene have been associated with a variety of human tumours and derivative cell lines, including Burkitt's lymphoma1,2, promyelocytic leukaemia3,4 and small cell lung cancer (SCLC)5. The N-myc gene, first detected by its homology to the second exon of the c-myc gene, is amplified and/or expressed in tumours or cell lines derived from neuroblastoma6-8, retinoblastoma9 and SCLC10. Here we describe a third myc-related gene (L-myc) cloned from SCLC DNA with homology to a small region of both the c-myc and N-myc genes. Human genomic DNA shows an EcoRI restriction fragment length polymorphism (RFLP) of L-myc defined by two alleles (10.0- and 6.6-kilobase (kb) EcoRI fragments), neither associated disproportionately with SCLC. Mouse and hamster DNAs exhibit a 12-kb EcoRI L-myc homologue, which indicates conservation of the gene in mammals. Gene mapping studies assign L-myc to human chromosome region Ip32, a location distinct from that of either c-myc1,11 or N-myc12 but associated with cytogenetic abnormalities in certain human tumours13. This L-myc sequence is amplified 10-20-fold in four SCLC cell line DNAs and in one SCLC tumour specimen taken directly from a patient. Either the 10.0- or 6.6-kb allele can be amplified and in heterozygotes only one of the two alleles was amplified in any SCLC genome. SCLC cell lines with amplified L-myc sequences express L-myc-derived transcripts not seen in SCLC with amplified c-myc or N-myc genes. In addition, some SCLCs without amplification also express L-myc-related transcripts. Together, these findings suggest an enlarging role for myc-related genes in human lung cancer and provide evidence for the concept of a myc family of proto-oncogenes.

Original languageEnglish (US)
Pages (from-to)69-73
Number of pages5
JournalNature
Volume318
Issue number6041
DOIs
StatePublished - Dec 1 1985

    Fingerprint

ASJC Scopus subject areas

  • General

Cite this

Nau, M. M., Brooks, B. J., Battey, J., Sausville, E., Gazdar, A. F., Kirsch, I. R., McBride, O. W., Bertness, V., Hollis, G. F., & Minna, J. D. (1985). L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer. Nature, 318(6041), 69-73. https://doi.org/10.1038/318069a0