Molecular alterations at 9q33.1 and polyploidy in asbestos-related lung cancer

Abstract

Purpose: Asbestos causes DNA damage and the fibers, together with tobacco smoke, have a synergistic effect on lung cancer risk. We recently identified 18 chromosomal regions that showed differences in DNA copy number between the lung tumors of asbestos-exposed and nonexposed patients. One of the previously identified asbestos-associated chromosomal regions at 9q was further analyzed for allelic imbalance and DNA copy number alterations (CNA) in the lung tumors of asbestos-exposed and nonexposed patients. In addition, the ploidy level of the tumors was studied.

Experimental design: Allelic imbalance was analyzed at 9q31.3-34.3 with 15 microsatellite markers in 52 lung tumor samples from asbestos-exposed and nonexposed patients. CNA at 9q32-34.3 were characterized by fluorescent in situ hybridization (FISH) with six bacterial artificial chromosome probes in 95 lung tumors. The ploidy level was analyzed in 100 lung tumors with FISH using three to five centromere probes.

Results: Allelic imbalance at 9q31.3-q34.3 was found in all asbestos-exposed patient tumors (100%, 17 of 17) compared with 64% (14 of 22) in the nonexposed cases (P = 0.005). The most significant difference was detected at 9q33.1 (P = 0.002). FISH results showed that also CNA were more frequent at 9q33.1 in the three major histologic types of non-small-cell lung tumors of exposed patients, and the association showed a dose-dependent trend (P = 0.03). Furthermore, we detected more frequent polyploidy among the exposed (48%, 28 of 58) than among the nonexposed (29%, 12 of 42) patient tumors (P < 0.05).

Conclusions: These results provide a basis for the development of a method to identify asbestos-related lung cancer on a molecular level.