CLINICAL IMPACT OF MYC FAMILY GENES IN LUNG CANCER

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Myc family (c-myc, N-myc, L-myc) DNA amplification was studied in tumor cell lines and tumor specimens from small cell lung cancer patients and correlated with their clinical course. A. Myc family DNA amplification was studied in 44 tumor cell lines established from small cell lung cancer patients treated at the NCI-Navy Medical Oncology Branch. The myc family DNA amplification was more common in cell lines established from chemotherapy treated patients (11/25) than from previously untreated patients (2/19). Patients whose cell lines had c-myc DNA amplification lived significantly shorter (median 33 weeks) compared to patients whose cell lines were not amplified for c-myc (median 53 weeks). No differences in survival was observed in treated patients whose cell lines were amplified for N-myc or L-myc. B. Twenty-eight tumor specimens from small cell lung cancer patients were studied. None of the 9 tumor specimens obtained from untreated patients had DNA amplification of any of myc family. Four of nineteen tumor specimens obtained from chemotherapy treated patients had DNA amplification of the myc family (3 N-myc, 1 L-myc). C. The c-myc gene was transfected into a small cell lung cancer cell line that does not express detectable c-myc mRNA and the transfected clones expressing c-myc mRNA grew faster, had a higher cloning efficiency, and had an altered large cell morphology. The myc family is important in understanding the biology of small cell lung cancer. DNA amplification of the genes is associated with treatment and c-myc is associated with shorter survival in patients and a more virulent phenotype in small cell lung cancer in vitro.