Accumulation of genomic alterations in 2p16, 9q33.1 and 19p13 in lung tumours of asbestos-exposed patients

Penny Nymark; Mervi Aavikko; Jussi Makila; Salla Ruosaari; Tuija Hienonen-Kempas; Harriet Wikman; Kaisa Salmenkivi; Risto Pirinen; Antti Karjalainen; Esa Vanhala; Eeva Kuosma; Sisko Anttila; Eeva Kettunen

doi:10.1016/j.molonc.2012.07.006

Accumulation of genomic alterations in 2p16, 9q33.1 and 19p13 in lung tumours of asbestos-exposed patients

Penny Nymark, Mervi Aavikko, Jussi Makila, Salla Ruosaari, Tuija Hienonen-Kempas, Harriet Wikman, Kaisa Salmenkivi, Risto Pirinen, Antti Karjalainen, Esa Vanhala, Eeva Kuosma, Sisko Anttila, Eeva Kettunen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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. Federation of European Biochemical Societies. Published by

Original language	English
Pages (from-to)	29-40
Journal	Molecular oncology
Volume	7
Issue number	1
DOIs	https://doi.org/10.1016/j.molonc.2012.07.006
Publication status	Published - Feb 2013

Keywords

Lung cancer
Asbestos exposure
Pulmonary epithelium
Allelic imbalance
DNA copy number alteration

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10.1016/j.molonc.2012.07.006Licence: Free access - publisher

Cite this

Nymark, P., Aavikko, M., Makila, J., Ruosaari, S., Hienonen-Kempas, T., Wikman, H., Salmenkivi, K., Pirinen, R., Karjalainen, A., Vanhala, E., Kuosma, E., Anttila, S., & Kettunen, E. (2013). Accumulation of genomic alterations in 2p16, 9q33.1 and 19p13 in lung tumours of asbestos-exposed patients. Molecular oncology, 7(1), 29-40. https://doi.org/10.1016/j.molonc.2012.07.006

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abstract = "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. Federation of European Biochemical Societies. Published by",

keywords = "Lung cancer, Asbestos exposure, Pulmonary epithelium, Allelic imbalance, DNA copy number alteration",

author = "Penny Nymark and Mervi Aavikko and Jussi Makila and Salla Ruosaari and Tuija Hienonen-Kempas and Harriet Wikman and Kaisa Salmenkivi and Risto Pirinen and Antti Karjalainen and Esa Vanhala and Eeva Kuosma and Sisko Anttila and Eeva Kettunen",

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Nymark, P, Aavikko, M, Makila, J, Ruosaari, S, Hienonen-Kempas, T, Wikman, H, Salmenkivi, K, Pirinen, R, Karjalainen, A, Vanhala, E, Kuosma, E, Anttila, S & Kettunen, E 2013, 'Accumulation of genomic alterations in 2p16, 9q33.1 and 19p13 in lung tumours of asbestos-exposed patients', Molecular oncology, vol. 7, no. 1, pp. 29-40. https://doi.org/10.1016/j.molonc.2012.07.006

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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 - Makila, 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

PY - 2013/2

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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. Federation of European Biochemical Societies. Published by

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. Federation of European Biochemical Societies. Published by

KW - Lung cancer

KW - Asbestos exposure

KW - Pulmonary epithelium

KW - Allelic imbalance

KW - DNA copy number alteration

U2 - 10.1016/j.molonc.2012.07.006

DO - 10.1016/j.molonc.2012.07.006

M3 - Article

C2 - 22901466

SN - 1574-7891

VL - 7

SP - 29

EP - 40

JO - Molecular oncology

JF - Molecular oncology

IS - 1

ER -