A new technique called spectral karyotyping has identified certain non-random chromosomal changes in smokers and patients with lung cancer and may provide the basis for a screening test that diagnoses precancerous lung lesions, according to an article in the September 1 issue of American Journal of Respiratory and Critical Care Medicine.

“The most successful way to reduce mortality in cancer is prevention,” said researcher and senior author Wilbur A. Franklin, MD, Professor of Pathology at the University of Colorado Health Sciences Center. “Our goal would be to develop screening techniques for lung lesions that could enable us to identify precancerous changes.”

Recent research suggested that the genetic changes that accompany lung cancer are not random, but are associated with specific chromosomal instabilities that may be indicative of future carcinomas. Researcher and lead author Marileila Varella-Garcia, MD, targeted these non-random chromosomal changes in the current study.

The technique called spectral karyotyping (SKY) was used to examine bronchial epithelium of 71 subjects?14 patients with lung cancer, 43 smokers at high risk for developing lung cancer and 14 healthy non-smokers-in the hope of identifying underlying genetic changes that might be hallmarks for cancer.

“It is critically important that we thoroughly understand the nature and timing of the cellular and genetic effects of tobacco smoke on bronchial epithelium in order to identify biomarkers and devise intervention strategies that might reduce the persisting morbidity and mortality from lung cancer,” said Varella-Garcia.

The researchers found a marked difference between the chromosomal abnormality index of never-smokers and that of high-risk smokers and patients with lung cancer.

“There’s a tremendous amount of chromosomal damage in smokers who don’t yet have cancer,” said Franklin. “Chromosomal abnormalities were observed in 82 percent of high-risk smokers and in all patients with carcinoma, regardless of their self-reported tobacco exposure.” Patients with cancer and high-risk smokers had nearly 23 and 15 times more chromosomal abnormalities, respectively, than never-smokers.

The most common changes among patients with cancer and high-risk smokers were gains on chromosomes 5, 7, 8 and 18.

The results from spectral karyotyping were confirmed by fluorescence in situ hybridization, which offers a less comprehensive view of genetic changes, but unlike spectral karyotyping, can detect genetic changes in interphase cells, which are readily available in sputum samples.

“Whereas spectral karyotyping is not a practical tool to directly apply to sputum, it does identify candidate chromosomal sequences that could improve the sensitivity of a FISH probe set for sputum screening and risk assessment,” wrote Franklin. “Improvement in sensitivity and perhaps automated processing and analysis could move a FISH-based assay toward clinical application.”

The researchers noted that their pilot study could not affirmatively determine whether the changes were predictive of eventual cancer, but their data point to an important avenue for future research. “It will be necessary to study larger cohorts for a longer interval,” they wrote, concluding, “SKY FISH is a feasible technique for comprehensive evaluation of the chromosomal changes in nonmalignant bronchial epithelial cells of high-risk individuals.”