title: DNA copy number loss and allelic imbalance at 2p16 in lung cancer associated with asbestos exposure.
abstract: Five to seven percent of lung tumours are estimated to occur because of occupational asbestos exposure. Using cDNA microarrays, we have earlier detected asbestos exposure-related genomic regions in lung cancer. The region at 2p was one of those that differed most between asbestos-exposed and non-exposed patients. Now, we evaluated genomic alterations at 2p22.1-p16.1 as a possible marker for asbestos exposure. Lung tumours from 205 patients with pulmonary asbestos fibre counts from 0 to 570 million fibres per gram of dry lung, were studied by fluorescence in situ hybridisation (FISH) for DNA copy number alterations (CNA). The prevalence of loss at 2p16, shown by three different FISH probes, was significantly increased in lung tumours of asbestos-exposed patients compared with non-exposed (P=0.05). In addition, a low copy number loss at 2p16 associated significantly with high-level asbestos exposure (P=0.02). Furthermore, 27 of the tumours were studied for allelic imbalances (AI) at 2p22.1-p16.1 using 14 microsatellite markers and also AI at 2p16 was related to asbestos exposure (P=0.003). Our results suggest that alterations at 2p16 combined with other markers could be useful in diagnosing asbestos-related lung cancer.
authors.affiliation: Health and Work Ability, Finnish Institute of Occupational Health, Helsinki, Finland. eeva.kettunen@ttl.fi
authors.forename: E
authors.initials: E
authors.lastname: Kettunen
authors.forename: M
authors.initials: M
authors.lastname: Aavikko
authors.forename: P
authors.initials: P
authors.lastname: Nymark
authors.forename: S
authors.initials: S
authors.lastname: Ruosaari
authors.forename: H
authors.initials: H
authors.lastname: Wikman
authors.forename: E
authors.initials: E
authors.lastname: Vanhala
authors.forename: K
authors.initials: K
authors.lastname: Salmenkivi
authors.forename: R
authors.initials: R
authors.lastname: Pirinen
authors.forename: A
authors.initials: A
authors.lastname: Karjalainen
authors.forename: E
authors.initials: E
authors.lastname: Kuosma
authors.forename: S
authors.initials: S
authors.lastname: Anttila