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Published on: April 21, 2022
Whole-Genome Comparative Copy Number Alteration Profiling between Malignant Pleural Mesothelioma and Asbestos-Induced
Tunç Tuncel1, Muzaffer Metintas2, A K Güntülü2
1Health Institutes of Turkey, Turkish Biotechnology Institute, Ankara, Turkey.
Abstract:
Malignant pleural mesothelioma (MPM) is rare and aggressive cancer. The most important risk factor for MPM is exposure to asbestos. In this study, we scanned the genomes of individuals MPM and asbestos-induced chronic pleuritis (AICP) to compare and determine copy number alterations (CNAs) between two asbestos-related diseases. We used high-resolution SNP arrays to compare CNA profiles between MPM (n = 55) and AICP (n = 18). DNAs extracted from pleural tissues in both groups. SNP array analysis revealed common losses at 1p, 3p, 6q, 9p, 13q, 14q, 15q, 16q, 22q and frequent gains at chromosomes 1, 3, 5, 7, 8, and 6p, 12q, 15q, 17p, 20q in MPMs (frequencies max 67%-min 30%; these alterations were not detected in AICPs. Besides detecting well-known MPM-associated CNAs, our high -resolution copy number profiling also detected comparatively rare CNAs for MPMs including losses like 9q33.3, 16q and gains of 1p, 1q, 3p, 3q, 6p, 7q, 15q, 12q, 17p, 20q at significant frequencies in the MPM cohort. We also observed Copy Number gains clustered on the NF2 locus in AICPs, whereas this region was commonly deleted in MPMs. According to this distinct genomic profiles between the two groups, AICPs genomes can be clearly distinguished from highly altered MPM genomes. Hence, we can suggest that SNP arrays can be used as a supporting diagnostic tool in terms of discriminating asbestos-related malignant disease such as MPM and benign pleural lesions, which can be challenging in most instances.
Insights
Genomic analysis reveals distinct copy number alterations in malignant pleural mesothelioma (MPM) compared to asbestos-induced chronic pleuritis (AICP). SNP arrays can help differentiate these asbestos-related pleural diseases.
Area of Science:
- Genomics
- Oncology
- Pulmonology
Background:
- Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer strongly linked to asbestos exposure.
- Asbestos exposure can also lead to benign pleural conditions like asbestos-induced chronic pleuritis (AICP).
- Differentiating between MPM and AICP can be diagnostically challenging.
Purpose of the Study:
- To compare copy number alterations (CNAs) between MPM and AICP using high-resolution SNP arrays.
- To identify distinct genomic profiles that can aid in distinguishing these asbestos-related pleural diseases.
- To explore the potential of SNP arrays as a diagnostic tool for asbestos-related pleural conditions.
Main Methods:
- High-resolution single nucleotide polymorphism (SNP) arrays were used to analyze DNA from pleural tissues.
- Genomic DNA was extracted from 55 MPM and 18 AICP patient samples.
- Copy number alteration profiles were compared between the two groups.
Main Results:
- MPM tissues showed frequent copy number losses (e.g., 1p, 3p, 6q) and gains (e.g., 1, 3, 5, 6p, 12q) not observed in AICP.
- Specific rare CNAs for MPM, including 9q33.3 losses and 1p, 1q gains, were identified.
- AICP tissues exhibited copy number gains at the NF2 locus, while MPM showed deletions in this region.
- Distinct genomic profiles clearly differentiated MPM from AICP.
Conclusions:
- Significant differences in copy number alterations exist between MPM and AICP.
- SNP array analysis can effectively distinguish between malignant and benign asbestos-related pleural diseases.
- SNP arrays show promise as a supportive diagnostic tool for challenging cases of asbestos-related pleural conditions.
Related Concept Videos
Pleural Disorders: Types and Brief Description
Comparing Copy Number Variations and SNPs
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...

