Evidence of gene amplification in the form of double minute chromosomes is frequently observed in lung cancer.
Amplification of cellular proto-oncogenes, important in tumor progression, has been correlated with a poor clinical outcome in a variety of human tumor types. Amplified genes are observed in two cytogenetically distinct entities, double minutes (DMs) and homogeneously staining regions (HSR). We examined 54 fresh lung tumor specimens obtained from patients with non-small cell lung cancer for cytogenetic evidence of gene amplification in the form of DMs. The majority of these patients had received no prior treatment. The cells were harvested within 24 hours after receiving the specimens, and the slides were stained with Giemsa to specifically look for DMs. We found DMs in 24 of 31 (77%) specimens that exhibited metaphase spreads. Similar incidences of DMs were found when histologic cell types, primary vs. non-primary tumors, and specimens from patients with prior treatment vs. no prior treatment were compared. Therefore, DMs occur frequently in non cultured lung tumor cells, providing evidence that gene amplification may be an important aspect of tumor behavior in patients with non-small cell lung carcinoma. Further investigation is warranted to identify the specific tumor-related genes located on these abnormal chromosomes. This also suggests that ongoing efforts to eliminate amplified drug-resistant genes or oncogenes contained on DMs in tumor cells may be relevant in patients with non-small cell lung cancer.
Nielsen
J L
JL
Institute for Cancer Research and Care, San Antonio, Texas 78229.
Walsh
J T
JT
Degen
D R
DR
Drabek
S M
SM
McGill
J R
JR
von Hoff
D D
DD
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002869:Chromosome Aberrations / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D008175:Lung Neoplasms / Q000235:genetics*