Dataset Information

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.

SUBMITTER: Nymark P

PROVIDER: S-EPMC5528398 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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

Nymark Penny P Aavikko Mervi M Mäkilä Jussi J Ruosaari Salla S Hienonen-Kempas Tuija T Wikman Harriet H Salmenkivi Kaisa K Pirinen Risto R Karjalainen Antti A Vanhala Esa E Kuosma Eeva E Anttila Sisko S Kettunen Eeva E

Molecular oncology 20120807 1

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 foun ...[more]

PMID: 22901466

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Project description:BackgroundNeuroblastoma is the most common pediatric malignancy with heterogeneous clinical behaviors, ranging from spontaneous regression to aggressive progression. Many studies have identified aberrations related to the pathogenesis and prognosis, broadly classifying neuroblastoma patients into high- and low-risk groups, but predicting tumor progression and clinical management of high-risk patients remains a big challenge.ResultsWe integrate gene-level expression, array-based comparative genomic hybridization and functional gene-interaction network of 145 neuroblastoma patients to detect potential driver genes. The drivers are summarized into a driver-gene score (DGscore) for each patient, and we then validate its clinical relevance in terms of association with patient survival. Focusing on a subset of 48 clinically defined high-risk patients, we identify 193 recurrent regions of copy number alterations (CNAs), resulting in 274 altered genes whose copy-number gain or loss have parallel impact on the gene expression. Using a network enrichment analysis, we detect four common driver genes, ERCC6, HECTD2, KIAA1279, EMX2, and 66 patient-specific driver genes. Patients with high DGscore, thus carrying more copy-number-altered genes with correspondingly up- or down-regulated expression and functional implications, have worse survival than those with low DGscore (P = 0.006). Furthermore, Cox proportional-hazards regression analysis shows that, adjusted for age, tumor stage and MYCN amplification, DGscore is the only significant prognostic factor for high-risk neuroblastoma patients (P = 0.008).ConclusionsIntegration of genomic copy number alteration, expression and functional interaction-network data reveals clinically relevant and prognostic putative driver genes in high-risk neuroblastoma patients. The identified putative drivers are potential drug targets for individualized therapy.ReviewersThis article was reviewed by Armand Valsesia, Susmita Datta and Aleksandra Gruca.

Dataset Information

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

Publications

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

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