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 journalArticleAcademicpeer-review

15 Citations (Web of Science)

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 languageEnglish
Pages (from-to)29-40
JournalMolecular oncology
Volume7
Issue number1
DOIs
Publication statusPublished - Feb 2013

Keywords

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

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