COMPARISON OF DNA COPY NUMBER CHANGES IN MALIGNANT MESOTHELIOMA, ADENOCARCINOMA AND LARGE-CELL ANAPLASTIC CARCINOMA OF THE LUNG

The differential diagnosis of mesothelioma, primary adenocarcinomas an d pleural metastases frequently causes problems. We have used the comp arative genomic hybridization (CGH) technique on 34 malignant mesothel iomas and 30 primary lung carcinomas (adenocarcinoma, including bronch oalveolar carcinoma and large-cell anaplastic carcinoma) to compare th eir copy number changes and to evaluate the use of CGH to distinguish between these two types of tumour. In mesothelioma, gains of genetic m aterial occurred as frequently as losses, whereas gains predominated o ver losses in carcinoma. In mesothelioma, the most frequent changes we re losses in 4q, 6q and 14q and gains in 15q and 7p, whereas gains in 8q, 1q, 7p, 5p and 6p were the most common changes in carcinoma. Ampli fication of KRAS2 was detected in two adenocarcinomas by Southern blot analysis. CGH showed gains in 12p in the same tumours. Statistically significant differences between the two types of tumour were detected in chromosomes X, 1, 2p, 4, 8q, 10q, 12q, 14q, 15q and 18q. When compa ring the frequency of gains and losses between mesothelioma and lung c arcinoma using discriminant analysis, the sensitivity of CGH to differ entiate mesotheliomas from lung carcinomas was 81% and the specificity 77%. The differences in DNA copy number changes between the two types of tumour suggest that they are genetically different tumour entities . Although CGH cannot be used as a definitive discriminatory method, w e were able to distinguish between mesothelioma and lung carcinoma in a large proportion of the abnormal cases.