Genomic changes of chromosomes 8p23.1 and 1q21: Novel mutations in malignant mesothelioma

Our plain-English summary of Genomic changes of chromosomes 8p23.1 and 1q21: Novel mutations in malignant mesothelioma, by G. Serio, L. Vimercati, A. Pennella, et al (Lung Cancer, 2018).

The study

• Authors: G. Serio, L. Vimercati, A. Pennella, M. Gentile, D. Cavone, A.L. Buonadonna, A. Scattone, F. Fortarezza, A. De Palma, A. Marzullo
• Journal: Lung Cancer
• Published: 2018;126:106-111
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Malignant mesothelioma is an aggressive malignancy of the thoracic cavity caused by prior asbestos exposure. In the peritoneum the mesothelioma is an extremely rare condition. In the present preliminary study, high-resolution array-comparative genomic hybridization (a-CGH) was performed to identify genetic imbalances in a series of malignant peritoneal mesothelioma cases.

Materials And Methods: Between 1990 and 2008, among the cases recorded in the Apulia Mesothelioma Register, we found 22 peritoneal mesothelioma cases. CGH-array was performed on samples from all patients.

Results: The CGH-array analysis revealed multiple chromosomal imbalances. Interestingly, deletion at 8p23.1 was observed in 12 cases. Furthermore, another novel deletion at 1q21 was present in 11. Often, 1q21 and 8p23.1 losses were present in the same patient (7 cases). Losses of BAP1 and CDKN2A loci were not detected.

Discussion: The region at 8p23.1 contains the beta-defensin gene cluster (DEF) and 1q21 contains ubiquitin conjugating enzyme E2 (UBE2Q1). We hypotesized that the loss of function of ubiquitination, as well as of the defensins, could play an important role in the initial development and subsequent progression of mesothelioma.

Copyright © 2018 Elsevier B.V. All rights reserved.

In plain English

This preliminary study looked for genetic changes in tumors from 22 people with malignant peritoneal mesothelioma (mesothelioma of the lining of the abdomen). The cases were recorded in the Apulia Mesothelioma Register in southern Italy between 1990 and 2008. All patients lived in the city of Bari, where asbestos was produced at the Fibronit factory. Asbestos exposure was well documented in 18 of the 22: occupational in 10, environmental in 7 and domestic in 1. The article does not name asbestos fiber types. Using a laboratory technique called array-comparative genomic hybridization, the authors found many chromosome gains and losses. A loss at chromosome region 8p23.1 appeared in 12 cases, 10 of them asbestos-exposed. A loss at 1q21 appeared in 11 cases, all but one with documented exposure. Both losses occurred together in 7 cases. Losses at the BAP1 and CDKN2A genes were not detected. The 8p23.1 region contains the beta-defensin gene cluster, and 1q21 contains the UBE2Q1 gene, which is involved in ubiquitination. The authors hypothesized that loss of function of the defensins and of ubiquitination could play an important role in the development and progression of mesothelioma. They said the results need further confirmation.

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: Preliminary laboratory genetic analysis (array-comparative genomic hybridization) of tumor samples from a series of malignant peritoneal mesothelioma cases
• Who was studied: 22 peritoneal mesothelioma cases recorded in the Apulia Mesothelioma Register (southern Italy), 1990 to 2008. All patients lived in Bari. The text gives ages 36 to 80 years at diagnosis (mean 61.6). There were 14 epithelioid, 5 biphasic and 3 sarcomatoid tumors.
• Exposure: Asbestos exposure was well documented in 18 of 22 cases. It was occupational in 10 (mean exposure 16.5 years), environmental in 7 (living near polluted sites) and domestic in 1. Patients lived in Bari, where asbestos was produced at the Fibronit factory. Fiber types are not specified.
• Main results:
  • Deletion at chromosome region 8p23.1 was found in 12 of the 22 cases, 10 of them with asbestos exposure
  • Deletion at 1q21 was found in 11 cases; only one of these lacked a documented history of asbestos exposure
  • Losses at both 1q21 and 8p23.1 were present in the same patient in 7 cases
  • Across the cases, chromosome deletions were less frequent than gains
  • Losses at the BAP1 and CDKN2A genes were not detected
  • In the one case given extra testing, BAP1 staining was strongly positive in tumor cell nuclei. FISH testing in that case showed normal CDKN2A and a homozygous deletion of 8p23.1.
  • The 8p23.1 region contains the beta-defensin gene cluster
  • The 1q21 region contains the UBE2Q1 gene, which plays a role in the conjugation and degradation of proteins
• The authors' conclusion: The authors hypothesized that loss of function of ubiquitination (linked to the UBE2Q1 gene at 1q21) and of the defensins (the beta-defensin gene cluster at 8p23.1) could play an important role in the initial development and progression of mesothelioma
• Limitations the authors state:
  • The authors state the results need further confirmation with more sensitive and specific molecular analysis focused on the 8p23.1 and 1q21 changes
  • BAP1 and CDKN2A status was checked by immunohistochemistry and FISH in only one case; the authors plan to investigate all cases

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Asbestos Exposure, Peritoneum, Mesothelioma, Peritoneal Mesothelioma, BAP1, CDKN2A.

Related studies

• Induction of micronuclei, hyperdiploidy and chromosomal breakage affecting the centric/pericentric regions of chromosomes 1 and 9 in human amniotic fluid cells after treatment with asbestos and ceramic fibers — E. Dopp, M. Schuler, et al. (1997)
• Comparative genomic hybridisation in malignant deciduoid mesothelioma — A. Scattone, A. Pennella, et al. (2006)
• Recurring loss involving chromosomes 1, 3, and 22 in malignant mesothelioma: possible sites of tumor suppressor genes — W.L. Flejter, F.P. Li, et al. (1989)
• Smoking enhances asbestos-induced genotoxicity, relative involvement of chromosome 1: a study using multicolor FISH with tandem labeling — M. Lohani, E. Dopp, et al. (2002)
• Interphase cytogenetics on paraffin sections of malignant pleural mesothelioma. A comparison to conventional karyotyping and flow cytometric studies — M. Tiainen, A. Hopman, et al. (1992)
• Metsovo-tremolite asbestos fibres: in vitro effects on mutation, chromosome aberration, cell transformation and intercellular communication — K. Athanasiou, S.H. Constantopoulos, et al. (1992)

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