Accumulation of genomic alterations in 2p16, 9q33.1 and 19p13 in lung tumours of asbestos-exposed patients.
We have previously demonstrated an association between genomic alterations in 19p13, 2p16, and 9q33.1 and asbestos exposure in patients' lung tumours. This study detected allelic imbalance (AI) in these regions in asbestos-exposed lung cancer (LC) patients' histologically normal pulmonary epithelium. We extended the analyses of tumour tissue to cover a large LC patient cohort and studied DNA copy number alteration (CNA) and AI in 19p13, 2p16, and 9q33.1 for the first time in combination. We found both CNA and AI in ≥2/3 of the regions to be significantly and dose-dependently (P < 0.001) associated with pulmonary asbestos fibre count. Twenty percent of the exposed patients' LC showed CNA in ≥2/3 of the regions, whereas none of the non-exposed patients' LC showed CNA in more than one region. AI was evident in 89% of the exposed and in only 26% of the non-exposed patients' LC. The genomic alterations in 19p13, 2p16, and 9q33.1 in compilation identified asbestos-exposed patients' lung tumours better than each of the regions alone. These alterations form the basis for the development of a combinatorial molecular assay that could be used to identify asbestos-related LC.
Health and Work Ability, Finnish Institute of Occupational Health, Topeliuksenkatu 41 aA, 00250 Helsinki, Finland. penny.nymark@ttl.fi
Penny
P
Nymark
Mervi
M
Aavikko
Jussi
J
Mäkilä
Salla
S
Ruosaari
Tuija
T
Hienonen-Kempas
Harriet
H
Wikman
Kaisa
K
Salmenkivi
Risto
R
Pirinen
Antti
A
Karjalainen
Esa
E
Vanhala
Eeva
E
Kuosma
Sisko
S
Anttila
Eeva
E
Kettunen
D001194:Asbestos / Q000633:toxicity*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics*
D001194:Asbestos