CGH analysis of radon‐induced rat lung tumors indicates similarities with human lung cancers

Dano, Laurent; Guilly, Marie Noëlle; Muleris, Martine; Morlier, Jean Paul; Altmeyer, Sandrine; Vielh, Philippe; El‐Naggar, Adel K.; Monchaux, G.; Dutrillaux, Bernard; Chevillard, Sylvie

doi:10.1002/1098-2264(2000)9999:9999<000::aid-gcc1000>3.3.co;2-s

Cited by 22 publications

(10 citation statements)

References 34 publications

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“…However, by classic CGH, the 2p23 gain in most cases was larger and contained 2p21 in half of the cases. This quite large region could thus be a target for further investigation because a region homologous to the human 2p21-25 has previously been reported to be amplified in radon-induced rat lung tumors (26). Otherwise 2p amplifications have rarely been described in non-SCLC.…”

Section: Resultsmentioning

confidence: 99%

Identification of Specific Gene Copy Number Changes in Asbestos-Related Lung Cancer

et al. 2006

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Asbestos is a well-known lung cancer-causing mineral fiber. In vitro and in vivo experiments have shown that asbestos can cause chromosomal damage and aberrations. Lung tumors, in general, have several recurrently amplified and deleted chromosomal regions. To investigate whether a distinct chromosomal aberration profile could be detected in the lung tumors of heavily asbestos-exposed patients, we analyzed the copy number profiles of 14 lung tumors from highly asbestosexposed patients and 14 matched tumors from nonexposed patients using classic comparative genomic hybridization (CGH). A specific profile could lead to identification of the underlying genes that may act as mediators of tumor formation and progression. In addition, array CGH analyses on cDNA microarrays (13,000 clones) were carried out on 20 of the same patients. Classic CGH showed, on average, more aberrations in asbestos-exposed than in nonexposed patients, and an altered region in chromosome 2 seemed to occur more frequently in the asbestos-exposed patients. Array CGH revealed aberrations in 18 regions that were significantly associated with either of the two groups. The most significant regions were 2p21-p16.3, 5q35.3, 9q33.3-q34.11, 9q34.13-q34.3, 11p15.5, 14q11.2, and 19p13.1-p13.3 (P < 0.005). Furthermore, 11 fragile sites coincided with the 18 asbestos-associated regions (P = 0.08), which may imply preferentially caused DNA damage at these sites. Our findings are the first evidence, indicating that asbestos exposure may produce a specific DNA damage profile. (Cancer Res 2006; 66(11): 5737-43)

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Section: Resultsmentioning

confidence: 99%

Identification of Specific Gene Copy Number Changes in Asbestos-Related Lung Cancer

et al. 2006

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“…Furthermore, the q-arm of chromosome 22 has been reported to be commonly lost in malignant mesothelioma, a cancer type closely linked to asbestos exposure (De Rienzo and Testa, 2000). Whereas, 2p amplifications have rarely been described in lung tumors, a region homologous to the human 2p21-p25 has previously been reported to be amplified in radon-induced rat lung tumors (Dano et al, 2000). Although 16p13.3 has been reported to be amplified rarely, it contains TSC2 gene, which has been described to be affected by LOH in 29% of lung adenocarcinomas (Takamochi et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Gene expression and copy number profiling suggests the importance of allelic imbalance in 19p in asbestos-associated lung cancer

et al. 2007

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Asbestos is a pulmonary carcinogen known to give rise to DNA and chromosomal damage, but the exact carcinogenic mechanisms are still largely unknown. In this study, gene expression arrays were performed on lung tumor samples from 14 heavily asbestos-exposed and 14 nonexposed patients matched for other characteristics. Using a two-step statistical analysis, 47 genes were revealed that could differentiate the tumors of asbestos-exposed from those of non-exposed patients. To identify asbestosassociated regions with DNA copy number and expressional changes, the gene expression data were combined with comparative genomic hybridization microarray data. As a result, a combinatory profile of DNA copy number aberrations and expressional changes significantly associated with asbestos exposure was obtained. Asbestosrelated areas were detected in 2p21-p16. 3, 3p21.31, 5q35.2-q35.3, 16p13.3, 19p13.3-p13.1 and 22q12.3-q13.1. The most prominent of these, 19p13, was further characterized by microsatellite analysis in 62 patients for the differences in allelic imbalance (AI) between the two groups of lung tumors. 79% of the exposed and 45% of the non-exposed patients (P ¼ 0.008) were found to be carriers of AI in their lung tumors. In the exposed group, AI in 19p was prevalent regardless of the histological tumor type. In adenocarcinomas, AI in 19p appeared to occur independently of the asbestos exposure.

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“…Random priming was performed using a Bioprime labeling kit (Invitrogen, Cergy Pontoise, France) according to the manufacturer's instructions with a modified dNTP pool containing 100 mM each of dATP, dGTP and dCTP; and 65 mM dTTP and 35 mM Biotin-16-dUTP (for the escape cell colonies' DNA) or DIG-11-dUTP (for the parental PROb reference DNA). Labeled probes were ethanol-precipitated with 50 mg of rat Cot-1 DNA (Applied Genetics Laboratories, Melbourne, FL, USA) and hybridized on normal rat metaphases as previously described (Dano et al, 2000). Biotin and digoxigenin probes were supplied by Avidin-FITC (Vector Laboratories, Burlingame, CA, USA) and anti-digoxigeninrhodamine antibodies by Roche Diagnostics, respectively.…”

Section: Comparative Genomic Hybridizationmentioning

confidence: 99%

Tumor cells can escape DNA‐damaging cisplatin through DNA endoreduplication and reversible polyploidy

Puig

Guilly

Bouchot

et al. 2008

Cell Biology International

237

216

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Cancer chemotherapy can induce tumor regression followed, in many cases, by relapse in the long-term. Thus this study was performed to assess the determinants of such phenomenon using an in vivo cancer model and in vitro approaches. When animals bearing an established tumor are treated by cisplatin, the tumor initially undergoes a dramatic shrinkage and is characterized by giant tumor cells that do not proliferate but maintain DNA synthesis. After several weeks of latency, the tumor resumes its progression and consists of small proliferating cells. Similarly, when tumor cells are exposed in vitro to pharmacological concentrations of cisplatin, mitotic activity stops initially but cells maintain DNA duplication. This DNA endoreduplication generates giant polyploid cells that then initiate abortive mitoses and can die through mitotic catastrophe. However, many polyploid cells survive for weeks as non-proliferating mono- or multi-nucleated giant cells which acquire a senescence phenotype. Prolonged observation of these cells sheds light on the delayed emergence of a limited number of extensive colonies which originate from polyploid cells, as demonstrated by cell sorting analysis. Theses colonies are made of small diploid cells which differ from parental cells by stereotyped chromosomal aberrations and an increased resistance to cytotoxic drugs. These data suggest that a multistep pathway, including DNA endoreduplication, polyploidy, then depolyploidization and generation of clonogenic escape cells can account for tumor relapse after initial efficient chemotherapy.

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CGH analysis of radon‐induced rat lung tumors indicates similarities with human lung cancers

Cited by 22 publications

References 34 publications

Identification of Specific Gene Copy Number Changes in Asbestos-Related Lung Cancer

Identification of Specific Gene Copy Number Changes in Asbestos-Related Lung Cancer

Gene expression and copy number profiling suggests the importance of allelic imbalance in 19p in asbestos-associated lung cancer

Tumor cells can escape DNA‐damaging cisplatin through DNA endoreduplication and reversible polyploidy

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