DNA copy number gains in malignant pleural mesothelioma

Our plain-English summary of DNA copy number gains in malignant pleural mesothelioma, by M. Furukawa, S. Toyooka, T. Hayashi, et al (Oncology Letters, 2015).

The study

• Authors: M. Furukawa, S. Toyooka, T. Hayashi, H. Yamamoto, N. Fujimoto, J. Soh, S. Hashida, K. Shien, H. Asano, K. Aoe, K. Okabe, H.I. Pass, K. Tsukuda, T. Kishimoto, S. Miyoshi
• Journal: Oncology Letters
• Published: 2015;10(5):3274-3278
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with an extremely poor prognosis. The incidence of MPM is increasing as a result of widespread exposure to asbestos. The molecular pathogenesis of MPM remains unclear. The present study analyzed the frequency of various genomic copy number gains (CNGs) in MPM using reverse transcription-quantitative polymerase chain reaction. A total of 83 primary MPMs and 53 primary lung adenocarcinomas were analyzed to compare the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2. In MPM, the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2 were detected in 12 (14.5%), 8 (9.6%), 5 (6.0%), 4 (4.8%) and 1 (1.2%) of the samples, respectively. In lung adenocarcinomas, the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2 were detected in 21 (39.6%), 12 (22.6%), 5 (9.4%), 10 (18.9%) and 0 (0.0%) of the samples, respectively. The CNGs of EGFR, KRAS and FGFR1 were significantly less frequent in the MPMs compared with the lung adenocarcinomas (P=0.0018, 0.048 and 0.018, respectively). Overall, the MPMs exhibited these CNGs less frequently compared with the lung adenocarcinomas (P=0.0002). The differences in CNGs between the two tumor types suggested that they are genetically different.

In plain English

This laboratory study compared genetic changes in two kinds of tumor removed at surgery: 83 malignant pleural mesotheliomas (57 of the epithelioid subtype) and 53 lung adenocarcinomas. The samples came from three Japanese hospitals and a US cancer center. The study did not report the patients' asbestos exposure. Using a PCR test on tumor DNA, the authors counted extra copies of five genes (copy number gains): EGFR, KRAS, MET, FGFR1 and SOX2. In the mesotheliomas, gains were found for EGFR in 12 (14.5%), KRAS in 8 (9.6%), MET in 5 (6.0%), FGFR1 in 4 (4.8%) and SOX2 in 1 (1.2%). In the lung adenocarcinomas, the figures were 21 (39.6%), 12 (22.6%), 5 (9.4%), 10 (18.9%) and 0 (0.0%). Gains in EGFR, KRAS and FGFR1 were significantly less frequent in mesothelioma. At least one gain was present in 19 of 83 mesotheliomas (22.9%) and in 29 of 53 adenocarcinomas (54.7%). No EGFR mutations were found in the mesotheliomas. The authors concluded that the differences suggested the two tumor types are genetically different.

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 comparison of gene copy number gains in surgically removed tumor specimens, using quantitative PCR on tumor DNA
• Who was studied: Surgically removed tumors: 83 malignant pleural mesotheliomas and 53 lung adenocarcinomas. The mesotheliomas were 57 epithelioid, 8 sarcomatoid, 15 biphasic, 2 desmoplastic and 1 lymphohistiocytic. All adenocarcinomas and 11 mesotheliomas came from Okayama University Hospital, 18 mesotheliomas from Yamaguchi-Ube Medical Center, 2 from Okayama Rosai Hospital and 52 from Karmanos Cancer Center (Detroit, USA). The Japanese samples were collected March 2002 to September 2011, and the US samples more than 10 years before.
• Exposure: Asbestos exposure was not studied or reported. The study measured copy number gains of EGFR, KRAS, MET, FGFR1 and SOX2 in tumor DNA, counting 3 or more copies as a gain in primary tumors, and also tested for EGFR mutations.
• Main results:
  • In the 83 mesotheliomas, copy number gains were found for EGFR in 12 (14.5%), KRAS in 8 (9.6%), MET in 5 (6.0%), FGFR1 in 4 (4.8%) and SOX2 in 1 (1.2%).
  • In the 53 lung adenocarcinomas, copy number gains were found for EGFR in 21 (39.6%), KRAS in 12 (22.6%), MET in 5 (9.4%), FGFR1 in 10 (18.9%) and SOX2 in 0 (0.0%).
  • Gains of EGFR, KRAS and FGFR1 were significantly less frequent in the mesotheliomas than in the lung adenocarcinomas (P=0.0018, 0.048 and 0.018).
  • At least one copy number gain was present in 19 of 83 mesotheliomas (22.9%), 10 of 57 epithelioid mesotheliomas (17.5%), 9 of 26 other-subtype mesotheliomas (34.6%) and 29 of 53 lung adenocarcinomas (54.7%).
  • All mesotheliomas and the epithelioid mesotheliomas each had gains less often than the lung adenocarcinomas (reported P=0.0002 and P=0.0001).
  • Three mesotheliomas, all epithelioid, had very high EGFR copy numbers (269, 62 and 14).
  • No EGFR mutations were found in the 83 mesotheliomas. EGFR mutations were found in 21 (39.6%) of the lung adenocarcinomas: 14 exon 19 deletions and 7 exon 21 (L858R) mutations.
• The authors' conclusion: The authors concluded that mesotheliomas showed these copy number gains less often than lung adenocarcinomas, and that the differences suggested the two tumor types are genetically different. They also suggested that copy number gain may not be a pivotal mechanism for activating oncogenes in mesothelioma.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Lung Adenocarcinoma, EGFR.

Related studies

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• Elevated PDGFRB gene copy number gain is prognostic for improved survival outcomes in resected malignant pleural mesothelioma — A.S. Tsao, N. Harun, et al. (2014)
• The degree of microRNA-34b/c methylation in serum-circulating DNA is associated with malignant pleural mesothelioma — T. Muraoka, J. Soh, et al. (2013)
• Comparison of DNA copy number changes in malignant mesothelioma, adenocarcinoma and large-cell anaplastic carcinoma of the lung — A.M. Björkqvist, L. Tammilehto, et al. (1998)
• 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)

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