Accumulation of genomic alterations in 2p16, 9q33.1 and 19p13 in lung tumours of asbestos-exposed patients
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Accumulation of genomic alterations in 2p16, 9q33.1 and 19p13 in lung tumours of asbestos-exposed patients. / Nymark, Penny; Aavikko, Mervi; Mäkilä, Jussi; Ruosaari, Salla; Hienonen-Kempas, Tuija; Wikman, Harriet; Salmenkivi, Kaisa; Pirinen, Risto; Karjalainen, Antti; Vanhala, Esa; Kuosma, Eeva; Anttila, Sisko; Kettunen, Eeva.
in: MOL ONCOL, Jahrgang 7, Nr. 1, 01.02.2013, S. 29-40.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Accumulation of genomic alterations in 2p16, 9q33.1 and 19p13 in lung tumours of asbestos-exposed patients
AU - Nymark, Penny
AU - Aavikko, Mervi
AU - Mäkilä, Jussi
AU - Ruosaari, Salla
AU - Hienonen-Kempas, Tuija
AU - Wikman, Harriet
AU - Salmenkivi, Kaisa
AU - Pirinen, Risto
AU - Karjalainen, Antti
AU - Vanhala, Esa
AU - Kuosma, Eeva
AU - Anttila, Sisko
AU - Kettunen, Eeva
N1 - Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
PY - 2013/2/1
Y1 - 2013/2/1
N2 - 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.
AB - 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.
KW - Asbestos
KW - Chromosomes, Human, Pair 13
KW - Chromosomes, Human, Pair 19
KW - Chromosomes, Human, Pair 2
KW - DNA Copy Number Variations
KW - Humans
KW - Lung Neoplasms
U2 - 10.1016/j.molonc.2012.07.006
DO - 10.1016/j.molonc.2012.07.006
M3 - SCORING: Journal article
C2 - 22901466
VL - 7
SP - 29
EP - 40
JO - MOL ONCOL
JF - MOL ONCOL
SN - 1574-7891
IS - 1
ER -
