Genome-wide analysis of abdominal and pleural malignant mesothelioma with DNA arrays reveals both common and distinct regions of copy number alteration

Our plain-English summary of Genome-wide analysis of abdominal and pleural malignant mesothelioma with DNA arrays reveals both common and distinct regions of copy number alteration, by A.C. Borczuk, J. Pei, R.N. Taub, et al (Cancer Biology & Therapy, 2016).

The study

• Authors: A.C. Borczuk, J. Pei, R.N. Taub, B. Levy, O. Nahum, J. Chen, K. Chen, J.R. Testa
• Journal: Cancer Biology & Therapy
• Published: 2016;17(3):328-35
• Cited by: 44 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) is an aggressive tumor arising from mesothelial linings of the serosal cavities. Pleural space is the most common site, accounting for about 80% of cases, while peritoneum makes up the majority of the remaining 20%. While histologically similar, tumors from these sites are epidemiologically and clinically distinct and their attribution to asbestos exposure differs. We compared DNA array-based findings from 48 epithelioid peritoneal MMs and 41 epithelioid pleural MMs to identify similarities and differences in copy number alterations (CNAs). Losses in 3p (BAP1 gene), 9p (CDKN2A) and 22q (NF2) were seen in tumors from both tumor sites, although CDKN2A and NF2 losses were seen at a higher rate in pleural disease (p<0.01). Overall, regions of copy number gain were more common in peritoneal MM, whereas losses were more common in pleural MM, with regions of loss containing known tumor suppressor genes and regions of gain encompassing genes encoding receptor tyrosine kinase pathway members. Cases with known asbestos causation (n = 32 ) were compared with those linked to radiation exposure (n = 9 ). Deletions in 6q, 14q, 17p and 22q, and gain of 17q were seen in asbestos-associated but not radiation-related cases. As reported in post-radiation sarcoma, gains outnumbered losses in radiation-associated MM. The patterns of genomic imbalances suggest overlapping and distinct molecular pathways in MM of the pleura and peritoneum, and that differences in causation (i.e., asbestos vs. radiation) may account for some of these site-dependent differences.

In plain English

This laboratory study compared DNA copy number changes (extra or missing stretches of chromosomes) in tumors from people with the epithelioid type of malignant mesothelioma. The authors analyzed 48 peritoneal (abdominal) tumors from Columbia University and 41 pleural tumors. Of the pleural tumors, 38 came from previously published Memorial Sloan-Kettering Cancer Center data and 3 from Columbia. Losses in regions containing the BAP1, CDKN2A and NF2 genes were seen at both sites. Losses of CDKN2A and NF2 were significantly more frequent in pleural tumors, but losses of BAP1 were not. Overall, losses were more common in pleural tumors and gains more common in peritoneal tumors. The authors also compared 32 cases with documented asbestos exposure with 9 cases that had prior radiation therapy for another cancer. Losses in parts of 22q, 14q and 6q, and gains in 17q, appeared in none of the 9 radiation cases but in 37.5% to 47.7% of the asbestos cases. The radiation cases showed multiple regions of gain. The authors concluded that these asbestos-linked changes occurred regardless of tumor site. They noted their series had only two post-radiation pleural cases.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory genetic study comparing DNA copy number alterations in tumor tissue: new SNP-array analysis of Columbia University samples compared with previously published pleural mesothelioma array data from Memorial Sloan-Kettering Cancer Center
• Who was studied: 89 patients with epithelioid malignant mesothelioma: 48 peritoneal cases from Columbia University and 41 pleural cases (38 from MSKCC published data, 3 from Columbia)
• Exposure: Asbestos exposure (no fiber type given), documented in 32 patients, compared with medical radiation therapy for a prior cancer in 9 patients. Among the 48 peritoneal cases, 12 were attributed to asbestos based on strong exposure history and 7 to radiation.
• Main results:
  • Losses in regions of chromosome arms 3p, 9p and 22q, containing BAP1, CDKN2A and NF2, were seen in both peritoneal and pleural tumors, at different rates.
  • Losses of these genes were less frequent in peritoneal than in pleural tumors. The difference was significant for CDKN2A and NF2 but not for BAP1.
  • Regions of loss were more common in pleural tumors, and gains were more frequent in peritoneal tumors.
  • In the peritoneal tumors, losses in NF2, BAP1 and CDKN2A were found, but only BAP1 loss occurred in more than 33% of cases.
  • Losses in 22q11.1-q11.21, 22q13.2-q13.31, 14q and 6q21-25.1, and gains in 17q, were each seen in 0 of 9 radiation cases, compared with 37.5%, 45.4%, 44.6%, 41.3% and 47.7% of asbestos-related cases, respectively.
  • The radiation-exposed group showed multiple regions of gain (including 1q, 3p, 3q and 5p), while losses predominated in the asbestos-related group.
• The authors' conclusion: The authors concluded that peritoneal and pleural tumors share a similar overall pattern of copy number changes, with differences in gains and losses. They found that deletions in 6q, 14q, 17p and 22q and gains in 17q were associated with asbestos causation regardless of disease site. They suggested that a subset of peritoneal mesotheliomas that is genetically similar to pleural tumors may correspond to the asbestos-caused group.
• Limitations the authors state:
  • The series included only two post-radiation pleural mesotheliomas.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Peritoneum, Attribution, Asbestos Exposure, Epithelioid, BAP1, CDKN2A, Tumor Suppressor Gene.

Related studies

• Genomic copy number alterations in 33 malignant peritoneal mesothelioma analyzed by comparative genomic hybridization array — P. Chirac, D. Maillet, et al. (2016)
• BAP1 Is Altered by Copy Number Loss, Mutation, and/or Loss of Protein Expression in More Than 70% of Malignant Peritoneal Mesotheliomas — N. Leblay, F. Leprêtre, et al. (2017)
• Genome-wide Gene-Asbestos Exposure Interaction Association Study Identifies a Common Susceptibility Variant on 22q13.31 Associated with Lung Cancer Risk — C.Y. Liu, I. Stücker, et al. (2015)
• CDKN2A copy number and p16 expression in malignant pleural mesothelioma in relation to asbestos exposure — E. Kettunen, S. Savukoski, et al. (2019)
• Combined Analysis of SNP Array Data Identifies Novel CNV Candidates and Pathways in Ependymoma and Mesothelioma — G. Wajnberg, B.S. Carvalho, et al. (2015)
• Loss of BAP1 expression is very rare in peritoneal and gynecologic serous adenocarcinomas and can be useful in the differential diagnosis with abdominal mesothelioma — J. Andrici, J. Jung, et al. (2016)

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