FISH Analysis of Crizotinib Target Genes ROS1/ALK/MET in Malignant Mesothelioma

Our plain-English summary of FISH Analysis of Crizotinib Target Genes ROS1/ALK/MET in Malignant Mesothelioma, by S. Salvi, S. Varesano, S. Boccardo, et al (Journal of Thoracic Oncology, 2017).

The study

• Authors: S. Salvi, S. Varesano, S. Boccardo, J.L. Ravetti, P.A. Canessa, M.P. Pistillo, P. Ferro, F. Fedeli, S. Roncella
• Journal: Journal of Thoracic Oncology
• Published: 2017;12(8):e116-e118
• Type of article: Letter
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this letter, the authors asked how many patients with malignant mesothelioma might benefit from crizotinib, a drug used in advanced non-small cell lung cancer with ROS1 or ALK gene rearrangement or MET gene amplification. Earlier, they had reported MET amplification in about 2% and high MET polysomy in 6.7% of mesothelioma patients. Here they examined ROS1 and ALK and studied MET in a larger series. They used fluorescence in situ hybridization (FISH) on 106 mesothelioma samples: 60 epithelioid, 34 sarcomatoid and 12 biphasic. Of the patients, 66% were men, and the median age was 64 years. Seventy-nine samples came from two commercial tissue microarrays (US Biomax), 16 from a pathology unit in Genoa and 11 from a histopathology unit in La Spezia, Italy. None of the 106 samples showed ROS1 or ALK rearrangement. Two samples, both epithelioid (1.9%), showed MET amplification. Six samples (5.7%; four epithelioid, one sarcomatoid, one biphasic) showed high MET polysomy. The authors described this as the first FISH analysis of ROS1 in mesothelioma. They noted that ROS1 rearrangement is also rare in lung cancer, so a larger series might find a few positive cases. They concluded that only MET can reasonably be considered a candidate target gene for selecting mesothelioma patients for crizotinib treatment.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This was a letter to the editor reporting a laboratory analysis of malignant mesothelioma tumor samples. The authors wanted to estimate how many patients might be candidates for crizotinib, a drug that acts on the products of three genes (ROS1, ALK and MET). Using fluorescence in situ hybridization (FISH), they examined 106 mesothelioma samples: 60 epithelioid, 34 sarcomatoid and 12 biphasic. Men made up 66% of the sample, and the median age was 64. None of the 106 samples showed ROS1 or ALK gene rearrangement. Two of the 106 samples, both epithelioid (1.9%), showed MET gene amplification. Six of the 106 (5.7%; four epithelioid, one sarcomatoid, one biphasic) showed high polysomy (extra copies) of MET. The authors said they could not exclude with absolute certainty that a larger series might find ROS1 rearrangement in a small number of cases. They concluded that only MET can reasonably be considered a candidate target gene for selecting mesothelioma patients for crizotinib. The letter does not address asbestos exposure.

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: Letter to the editor reporting a laboratory (FISH) analysis of mesothelioma tumor samples
• Who was studied: 106 malignant mesothelioma samples (60 epithelioid, 34 sarcomatoid, 12 biphasic); 66% from men; median age 64 years
• Exposure: No asbestos or other environmental exposure was studied. The study examined the status of the ROS1, ALK and MET genes in tumor samples.
• Main results:
  • None of the 106 mesothelioma samples (0%) showed ROS1 or ALK gene rearrangement
  • Two of the 106 samples, both epithelioid (1.9%), showed MET gene amplification
  • Six of 106 samples (four epithelioid, one sarcomatoid, one biphasic; 5.7%) showed high polysomy of MET, with six to 10 MET spots in about 60% to 80% of tumor cells
  • The MET findings confirmed percentages the authors had reported in an earlier letter
• The authors' conclusion: The authors concluded that ROS1 does not seem to be a candidate target for crizotinib in mesothelioma, and that only MET can reasonably be considered a candidate target gene for selecting mesothelioma patients for crizotinib
• Limitations the authors state:
  • Because ROS1 translocation is infrequent even in lung cancer, the authors could not exclude with absolute certainty that a larger series would find ROS1 rearrangement in a small number of mesothelioma 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: Fluorescence In Situ Hybridization (FISH), ROS1, Malignant Mesothelioma, Non-Small Cell Lung Cancer, Mesothelioma, Epithelioid, Sarcomatoid, Biphasic Mesothelioma.

Related studies

• Case report: targeted therapy of malignant pleural mesothelioma with anaplastic lymphoma kinase receptor tyrosine kinase gene fusion mutation by crizotinib — Y. Wu, Y. Zhao, et al. (2024)
• MET Gene Status in Malignant Mesothelioma Using Fluorescent In Situ Hybridization — S. Varesano, S. Salvi, et al. (2016)
• Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of the dl922-947 Oncolytic Virus in Malignant Mesothelioma Cell Lines — C.A. Iannuzzi, P. Indovina, et al. (2020)
• Evaluation of RET Gene Rearrangement by Fluorescence In Situ Hybridization in Malignant Mesothelioma — S. Salvi, J.L. Ravetti, et al. (2018)
• Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells — M. Yamaji, A. Ota, et al. (2017)
• Targeted inhibition of multiple receptor tyrosine kinases in mesothelioma — W.B. Ou, C. Hubert, et al. (2011)

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