DNA copy number loss and allelic imbalance at 2p16 in lung cancer associated with asbestos exposure

Five to seven percent of lung tumours are estimated to occur because of occupational asbestos exposure. Using cDNA microarrays, we have earlier detected asbestos exposure-related genomic regions in lung cancer. The region at 2p was one of those that differed most between asbestos-exposed and non-exposed patients. Now, we evaluated genomic alterations at 2p22.1-p16.1 as a possible marker for asbestos exposure. Lung tumours from 205 patients with pulmonary asbestos fibre counts from 0 to 570 million fibres per gram of dry lung, were studied by fluorescence in situ hybridisation (FISH) for DNA copy number alterations (CNA). The prevalence of loss at 2p16, shown by three different FISH probes, was significantly increased in lung tumours of asbestos-exposed patients compared with non-exposed (P=0.05). In addition, a low copy number loss at 2p16 associated significantly with high-level asbestos exposure (P=0.02). Furthermore, 27 of the tumours were studied for allelic imbalances (AI) at 2p22.1–p16.1 using 14 microsatellite markers and also AI at 2p16 was related to asbestos exposure (P=0.003). Our results suggest that alterations at 2p16 combined with other markers could be useful in diagnosing asbestos-related lung cancer

Association of chromosome 19 to lung cancer genotypes and phenotypes

et al.The Chromosome 19 Consortium, a part of the Chromosome-Centric Human Proteome Project (C-HPP, http://​www.​C-HPP.​org), is tasked with the understanding chromosome 19 functions at the gene and protein levels, as well as their roles in lung oncogenesis. Comparative genomic hybridization (CGH) studies revealed chromosome aberration in lung cancer subtypes, including ADC, SCC, LCC, and SCLC. The most common abnormality is 19p loss and 19q gain. Sixty-four aberrant genes identified in previous genomic studies and their encoded protein functions were further validated in the neXtProt database (http://​www.​nextprot.​org/​). Among those, the loss of tumor suppressor genes STK11, MUM1, KISS1R (19p13.3), and BRG1 (19p13.13) is associated with lung oncogenesis or remote metastasis. Gene aberrations include translocation t(15, 19) (q13, p13.1) fusion oncogene BRD4-NUT, DNA repair genes (ERCC1, ERCC2, XRCC1), TGFβ1 pathway activation genes (TGFB1, LTBP4), Dyrk1B, and potential oncogenesis protector genes such as NFkB pathway inhibition genes (NFKBIB, PPP1R13L) and EGLN2. In conclusion, neXtProt is an effective resource for the validation of gene aberrations identified in genomic studies. It promises to enhance our understanding of lung cancer oncogenesis.The work was supported by Zhongshan Distinguished Professor Grant (XDW), The National Nature Science Foundation of China (91230204, 81270099, 81320108001, 81270131, 81300010), The Shanghai Committee of Science and Technology (12JC1402200, 12431900207, 11410708600, 14431905100), Operation funding of Shanghai Institute of Clinical Bioinformatics, and Ministry of Education, Academic Special Science and Research Foundation for PhD Education (20130071110043). MF is supported by grant FIS14/01538 (ISCIII- Fondos FEDER EU) and Proteomics Units at CIC belongs to ProteoRed-PRB2 (PT13-001, ISCIII, Fondos FEDER-EU).Peer Reviewe