Role of NF2 Mutation in the Development of Eleven Different Cancers

Our plain-English summary of Role of NF2 Mutation in the Development of Eleven Different Cancers, by S.H. Nouri, V. Nitturi, E. Ledbetter, et al (Cancers, 2024).

The study

• Authors: S.H. Nouri, V. Nitturi, E. Ledbetter, C.W. English, S. Lau, T.J. Klisch, A.J. Patel
• Journal: Cancers
• Published: 2024;17(1)
• Type of article: Review
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background/Objectives: With the rise in prevalence of diagnostic genetic techniques like RNA sequencing and whole exome sequencing (WES), as well as biological treatment regiments for cancer therapy, several genes have been implicated in carcinogenesis. This review aims to update our understanding of the Neurofibromatosis 2 (NF2) gene and its role in the pathogenesis of various cancers. Methods: A comprehensive search of five online databases yielded 43 studies that highlighted the effect of sporadic NF2 mutations on several cancers, including sporadic meningioma, ependymoma, schwannoma, mesothelioma, breast cancer, hepatocellular carcinoma, prostate cancer, glioblastoma, thyroid cancer, and melanoma. Of note were key biological pathways implicated in cancer formation resulting from sporadic NF2 mutations. Results: NF2 gene mutations are implicated in over 11 different cancers, including several CNS tumors, soli-organ tumors, and skin cancer. NF2 acts as a driver mutation in some cancers, as a non-driver mutation in some cancers, and has simple associated mutations with other cancers. In terms of biological pathway involvement, 8 of the 11 cancers with NF2 mutations show evidence of Hippo signaling cascade involvement. Conclusions: Several cancers characterized by mutations in the NF2 gene have associations with the Hippo signaling pathway. However, future studies remain to be done to further elucidate the role of the Hippo signaling pathway in the carcinogenesis of human NF2-mutant tumors. The findings of this review provide insights into the role of NF2 mutations in cancers, Hippo signaling in NF2-mutant cancers, and current gaps in our knowledge regarding the two.

In plain English

This article was a literature review of how mutations in the NF2 gene, which normally acts as a tumor suppressor, relate to eleven kinds of cancer, including mesothelioma. According to the article's abstract, a search of five online databases found 43 studies. The included studies used human and mouse cells and models. The review did not assess asbestos exposure or estimate cancer risks from any exposure. The authors classed NF2 as a 'driver' mutation in meningioma, schwannoma, ependymoma, mesothelioma and renal cell carcinoma. They classed it as a 'non-driver' mutation in breast cancer, hepatocellular carcinoma and melanoma, and as an 'associated' mutation in glioblastoma, prostate cancer and thyroid cancer. They reported that 8 of the 11 cancers showed some involvement of a cell-growth control system called the Hippo signaling pathway. For mesothelioma, the review described earlier work reporting NF2 mutations in around 30% of malignant mesotheliomas. It also described a study in which NF2-mutant malignant pleural mesothelioma cells showed a deficiency in B-cell receptor signaling rather than Hippo-related changes. The authors concluded that there is no consensus on the pathway involved in NF2-mutant mesothelioma and that further studies are needed.

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: Literature review (not original research); the abstract reports 43 studies found through a search of five online databases
• Who was studied: Published experimental studies of NF2-mutant tumors in human cells and in mouse cells and models, covering eleven cancer types
• Exposure: Not applicable: the review concerns NF2 gene mutations. It did not assess asbestos exposure or estimate exposure-related cancer risks. It mentions laboratory treatments in cited cell studies, such as cadmium/zinc toxicity and hydrogen peroxide.
• Main results:
  • Across the 11 cancers reviewed, 8 were described as having NF2 mutations and some degree of Hippo signaling pathway modulation
  • The authors classed NF2 as a driver mutation in meningioma, schwannoma, ependymoma, mesothelioma and renal cell carcinoma
  • NF2 was classed as a non-driver mutation in breast cancer, hepatocellular carcinoma and melanoma
  • NF2 was classed as a simple associated mutation in glioblastoma, prostate cancer and thyroid cancer
  • Citing earlier studies, the review reported that around 30% of malignant mesotheliomas have been identified with somatic NF2 mutations
  • The review described an earlier analysis of 75 human lung cancer cell lines (38 small cell, 34 non-small cell, 3 carcinoid) that found no NF2 mutants, while NF2 mutations were found in mesotheliomas
  • In a cited study of human malignant pleural mesothelioma cells, NF2-mutant cells were not associated with changes in phospho-YAP levels and instead showed a deficiency in the B-cell receptor signaling pathway
• The authors' conclusion: The authors concluded that several NF2-mutant cancers are associated with the Hippo signaling pathway, but that further studies are needed to clarify its role. For mesothelioma, they stated that NF2 mutations are characteristic of these tumors, that no consensus exists on the pathway involved, and that further studies are needed.
• Limitations the authors state:
  • The authors stated there is a lack of studies on NF2-mutated ependymomas, so Hippo involvement there is unclear
  • The authors stated that no consensus has been reached on the biological pathway involved in NF2-mutant mesothelioma
  • The authors stated that the functional effects of different NF2 mutations have not yet been explored

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Mesothelioma, Carcinoma, Hippo Signaling Pathway.

Related studies

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• Germline mutation of Bap1 accelerates development of asbestos-induced malignant mesothelioma — J. Xu, Y. Kadariya, et al. (2014)
• Development of unenhanced CT-based imaging signature for BAP1 mutation status prediction in malignant pleural mesothelioma: Consideration of 2D and 3D segmentation — X.J. Xie, S.Y. Liu, et al. (2021)
• Intrahepatic cholangiocarcinoma development in a patient with a novel BAP1 germline mutation and low exposure to asbestos — G. Brandi, M. Deserti, et al. (2020)
• Asbestos as a systemic carcinogen: the evidence from eleven cohorts — J.R. Goldsmith (1982)
• Influence of inter-observer delineation variability on radiomics stability in different tumor sites — M. Pavic, M. Bogowicz, et al. (2018)

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