Genomic copy number alterations in 33 malignant peritoneal mesothelioma analyzed by comparative genomic hybridization array

Our plain-English summary of Genomic copy number alterations in 33 malignant peritoneal mesothelioma analyzed by comparative genomic hybridization array, by P. Chirac, D. Maillet, F. Leprêtre, et al (Human Pathology, 2016).

The study

• Authors: P. Chirac, D. Maillet, F. Leprêtre, S. Isaac, O. Glehen, M. Figeac, L. Villeneuve, J. Péron, F. Gibson, F. Galateau-Sallé, F.N. Gilly, M. Brevet
• Journal: Human Pathology
• Published: 2016;55:72-82
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant peritoneal mesotheliomas (MPM) are rare, accounting for approximately 8% of cases of mesothelioma in France. We performed comparative genomic hybridization (CGH) on frozen MPM samples using the Agilent Human Genome CGH 180 K array. Samples were taken from a total of 33 French patients, comprising 20 men and 13 women with a mean (range) age of 58.4 (17-76) years. Asbestos exposure was reported in 8 patients (24.2%). Median (range) overall survival (OS) was 39 (0-119) months. CGH analysis demonstrated the presence of chromosomal instability in patients with MPM, with a genomic pattern that was similar to that described for pleural mesothelioma, including the loss of chromosomal regions 3p21, 9p21, and 22q12. In addition, novel genomic copy number alterations were identified, including the 15q26.2 region and the 8p11.22 region. Median OS was associated with a low peritoneal cancer index (P=.011), epithelioid subtype (P=.038), and a low number of genomic aberrations (P=.015), all of which constitute good prognostic factors for MPM. Our results provide new insights into the genetic and genomic background of MPM. Although pleural and peritoneal mesotheliomas have different risk factors, different therapeutics, and different prognosis; these data provide support to combine pleural and peritoneal mesothelioma in same clinical assays.

Copyright © 2016 Elsevier Inc. All rights reserved.

In plain English

This laboratory study analyzed tumor DNA from 33 French patients with malignant peritoneal mesothelioma (20 men, 13 women). The samples were collected at a Lyon cancer institute between 1998 and 2014. The authors used array comparative genomic hybridization to find chromosome regions that were lost or gained. Asbestos exposure was reported for 8 patients (24.2%). The article does not name fiber types or say how exposure was assessed. All tumors showed alterations. Loss of the 3p21 region, which contains the BAP1 gene, occurred in 20 tumors (60.6%). Tumors had more losses than gains in 7 of 8 asbestos-exposed patients (87.5%), compared with 8 of 25 unexposed patients (32%) (p=0.01). Survival did not differ significantly by asbestos exposure. Longer survival was associated with a lower peritoneal cancer index, the epithelioid tumor type and fewer genetic alterations. The authors concluded that peritoneal and pleural mesothelioma share a similar pattern of alterations. They noted that their sample was too small to reliably test whether asbestos exposure was linked to loss of the CDKN2A gene.

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 genomic analysis (array comparative genomic hybridization) of tumor samples from a series of patients, with survival analysis
• Who was studied: 35 frozen peritoneal mesothelioma samples collected between 1998 and 2014 at Hospices Civils de Lyon, France. Two were excluded for low tumor content, leaving 33 patients: 20 men and 13 women, median age 63 (range 17 to 76). Patients were treated with cytoreductive surgery, most of them also with heated intraperitoneal chemotherapy (HIPEC).
• Exposure: Reported asbestos exposure (yes or no) in 8 of 33 patients. Fiber types, jobs and doses were not given.
• Main results:
  • Copy number alterations were found in all 33 tumors, with slightly more losses (1067) than gains (976).
  • The proportion of patients whose tumors had more losses than gains was higher among asbestos-exposed patients (7/8; 87.5%) than among unexposed patients (8/25; 32%), p=0.01.
  • The authors reported that asbestos exposure was correlated with a higher number of deleted genes (p=0.0001).
  • No significant differences in overall survival were seen by gender or by asbestos exposure.
  • The most common focal deletion, at the 3p21 region (containing BAP1, RASSF1, CTNNB1 and DUSP7), was found in 20 of 33 tumors (60.6%). BAP1 itself was deleted in 14 tumors (42.4%).
  • CDKN2A was deleted in 11 tumors (33.3%), including two homozygous deletions. NF2 was deleted in 7 tumors (21.2%).
  • A deletion at 8p11.22 containing ADAM3 was found in 19 tumors (57.6%). The authors described it as a novel region.
  • Median survival was 119 months for patients with a peritoneal cancer index of 28 or less (n=9) and 22 months for those with 29 or more (n=18), p=0.011.
  • Median survival was 71 months for epithelioid tumors and 8 months for non-epithelioid tumors (n=6), p=0.038.
  • Median survival was 83 months for patients with fewer than 40 alterations (n=17) and 32 months for those with more than 40 (n=16), p=0.015.
  • Median survival was 39 months for patients who received HIPEC (n=27) and 1.2 months for those who did not (n=6), p=0.003.
• The authors' conclusion: The authors concluded that, despite different epidemiological and clinical features, peritoneal and pleural mesothelioma showed a similar pattern of copy number alterations, including loss of 3p21, 9p21 and 22q12.
• Limitations the authors state:
  • The sample size was too small to reach reliable statistical significance for a link between asbestos exposure and CDKN2A loss (p=0.39). The authors said a larger multicenter cohort is needed.

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: Peritoneal Mesothelioma, Mesothelioma, Asbestos Exposure, Overall Survival, Pleural Mesothelioma, Peritoneal Cancer Index (PCI), Epithelioid, Prognosis.

Related studies

• 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 analysis of abdominal and pleural malignant mesothelioma with DNA arrays reveals both common and distinct regions of copy number alteration — A.C. Borczuk, J. Pei, et al. (2016)
• Comparative genetic analysis of a rare synchronous collision tumor composed of malignant pleural mesothelioma and primary pulmonary adenocarcinoma — T. Naka, Y. Hatanaka, et al. (2016)
• Applications of array-CGH for lung cancer — K.J. Craddock, W.L. Lam, et al. (2013)
• Fluorescence in situ hybridization (FISH) provides estimates of minute and interstitial BAP1, CDKN2A, and NF2 gene deletions in peritoneal mesothelioma — S. Brich, F. Bozzi, et al. (2020)
• Genomic gains and losses in malignant mesothelioma demonstrated by FISH analysis of paraffin-embedded tissues — M. Takeda, T. Kasai, et al. (2012)

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