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


METHODS
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.
Nymark
Penny
P
Health and Work Ability, Good Practices and Competence, and Work Environment Development, Finnish Institute of Occupational Health, Topeliuksenkatu 41 aA, 00250 Helsinki, Finland.
Kettunen
Eeva
E
Aavikko
Mervi
M
Ruosaari
Salla
S
Kuosma
Eeva
E
Vanhala
Esa
E
Salmenkivi
Kaisa
K
Pirinen
Risto
R
Karjalainen
Antti
A
Knuutila
Sakari
S
Wikman
Harriet
H
Anttila
Sisko
S
D000368:Aged; D000483:Alleles; D001194:Asbestos / Q000009:adverse effects*; D002869:Chromosome Aberrations; D022202:Chromosomes, Artificial, Bacterial; D002899:Chromosomes, Human, Pair 9; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D011123:Polyploidy
D001194:Asbestos