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

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.

Malignant cells from pleural fluids in malignant mesothelioma patients reveal novel mutations

“…Warranting further examination are the novel observations that significant losses occur in regions 19p13.3, 1p36.32 and 8p23.1. While alterations in 8p23.1, 1p36 and 19p13 have been observed in some cases of MM, our study was able to identify alterations in these regions to a high statistical significance [32][33][34][35]. The significance of these deleted regions in this study highlights the importance of these regions and the need for further investigation into the possible relevance of the genes found within.…”

Association of chromosome 19 to lung cancer genotypes and phenotypes

“…The damage was detected in 19p13.3-p13.1. Furthermore, allelic imbalance of 19p13 was detected in 79 % of the asbestos exposed and 45 % of the nonexposed lung cancer patients [35,36].…”

Asbestos, asbestosis, and cancer, the Helsinki criteria for diagnosis and attribution 2014: recommendations

“…A combination of three chromosome abnormalities (2p16, 9p33.1, and 19p13) gave a clear dose-response between pulmonary fibre count and either allelic imbalance or copy number alteration or both in at least two of the regions, with a very high specificity when the three regions were combined (24). Additional international multicenter studies with standardized methodology for molecular assays and exposure assessment are necessary before these biomarkers can be applied to support causal attribution in individual cases.…”