Tumor suppressor gene alterations in patients with malignant mesothelioma due to environmental asbestos exposure in Turkey

Journal of Carcinogenesis. 2006 Aug 22;5:23. [Link]

Esra Tug¹, Tuncer Tug² , Halit Elyas³ , Mehmet Coskunsel⁴ and Salih Emri⁵

¹Department of Medical Genetics, Abant Izzet Baysal University, Izzet Baysal Medical School, Bolu, Turkey
²Department of Chest Diseases; Abant Izzet Baysal University, Izzet Baysal Medical School, Bolu, Turkey
³Firat University Medical School, Department of Medical Biology, Elazig, Turkey
⁴Dicle University Medical School, Department of Chest Diseases, Diyarbakir, Turkey
⁵Hacettepe University Medical School, Department of Chest Diseases, Ankara, Turkey

Abstract

Background: Environmental asbestos exposure can cause the grave lung and pleura malignancies with a high mortality rate, and it is also associated with increased rate of other organ malignancies. Asbestos exposure can develop genotoxic effects and damage in the pleura and lungs.

Objective: In this study, we aimed to determine tumor suppressor gene (TSG) loss in genomic DNA which was isolated from pleural fluid and blood samples of patients with Malignant Pleural Mesothelioma (MPM) due to environmental asbestos exposure.

Design and patients: Prospective study of period from 2001 to 2003 in 17 patients with MPM.

Methods: A total of 12 chromosomal regions were researched by comparing genomic DNA samples isolated from blood and pleural effusion (using PCR, and polyacrilamid gel electrophoresis denaturizing), on 2 different chromosomes which have 9 different polymorphic determinants at 6q and 3 different polymorphic determinants at 9p using molecular genetic methods on 13 patients clinico-pathologically diagnosed MPM.

Results: Loss of Heterozygosity (LOH) was determined at D6S275 in one patient, at D6S301 in another, at D6S474 in 2, at ARG1 in 2, at D6S1038 in 2 and at D6S1008 in 3 patients. In 7 (54%) of the13 patients, we found LOH in at least one site. No LOH was determined at any informative loci in 6 patients. Of the 13 patients, no investigated markers were determined at 9p.

Conclusion: In this study, genomic DNA samples obtained from MPM patients with asbestos exposure revealed that they contained important genotoxic damage. We found no other study on this subject at molecular level in pleural effusion either in Turkey or in the med-line literature. We believe that this study will provide important support for other research into molecular-genetic variations, both on this subject and other malignancies, and may also constitute a base for early diagnosis and gene therapy research in the future.