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

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 lymphoma 1,2 , promyelocytic leukaemia 3,4 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 neuroblastoma 6–8 , retinoblastoma 9 and SCLC 10 . 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 Eco RI restriction fragment length polymorphism (RFLP) of L- myc defined by two alleles (10.0- and 6.6-kilobase (kb) Eco RI fragments), neither associated disproportionately with SCLC. Mouse and hamster DNAs exhibit a 12-kb Eco RI 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- myc 1,11 or N- myc 12 but associated with cytogenetic abnormalities in certain human tumours 13 . 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.