Transition of a vestibular schwannoma to a malignant peripheral nerve sheath tumor with loss of H3K27 trimethylation after radiosurgery—a case report and review of the literature

Behling, Felix; Bersali, Imane; Santacroce, Antonio; Hempel, Johann; Kandilaris, Kosmas; Schittenhelm, Jens; Tatagiba, Marcos

doi:10.1007/s10143-021-01620-3

Cited by 6 publications

(5 citation statements)

References 51 publications

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“…Further, the study of familial schwannomatosis was critical in the discovery of the role of SWI/SNF LOF in tumorigenesis. It is important to note that schwannomas are dynamic tumors that can transition to MPNST with different clinical characteristics and potentially a different underlying biology that may be more reminiscent of other malignant tumors in this same category [179]. It is possible that ERV expression plays a critical role in this malignant transformation and represents an interesting area for future investigation.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Regulation in Primary CNS Tumors: An Opportunity to Bridge Old and New WHO Classifications

Dang

Rosenblum

Shah

et al. 2023

Cancers

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Originally approved in 1979, a specific grading classification for central nervous system (CNS) tumors was devised by the World Health Organization (WHO) in an effort to guide cancer treatment and better understand prognosis. These “blue books” have since undergone several iterations based on tumor location, advancements in histopathology, and most recently, diagnostic molecular pathology in its fifth edition. As new research methods have evolved to elucidate complex molecular mechanisms of tumorigenesis, a need to update and integrate these findings into the WHO grading scheme has become apparent. Epigenetic tools represent an area of burgeoning interest that encompasses all non-Mendelian inherited genetic features affecting gene expression, including but not limited to chromatin remodeling complexes, DNA methylation, and histone regulating enzymes. The SWItch/Sucrose non-fermenting (SWI/SNF) chromatin remodeling complex is the largest mammalian family of chromatin remodeling proteins and is estimated to be altered in 20–25% of all human malignancies; however, the ways in which it contributes to tumorigenesis are not fully understood. We recently discovered that CNS tumors with SWI/SNF mutations have revealed an oncogenic role for endogenous retroviruses (ERVs), remnants of exogenous retroviruses that integrated into the germline and are inherited like Mendelian genes, several of which retain open reading frames for proteins whose expression putatively contributes to tumor formation. Herein, we analyzed the latest WHO classification scheme for all CNS tumors with documented SWI/SNF mutations and/or aberrant ERV expression, and we summarize this information to highlight potential research opportunities that could be integrated into the grading scheme to better delineate diagnostic criteria and therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Epigenetic Regulation in Primary CNS Tumors: An Opportunity to Bridge Old and New WHO Classifications

Dang

Rosenblum

Shah

et al. 2023

Cancers

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“… 9–11 Finally, while radiosurgery has been utilized, it does not result in complete tumor resection and is associated with significant concerns regarding complications including malignant transformation. 12 , 13 The debilitation and suffering endured by individuals with schwannoma (as well as their families), in combination with the paucity of therapeutic options, makes the treatment of schwannoma a major unmet medical need.…”

Section: Introductionmentioning

confidence: 99%

Culture of attenuated Salmonella Typhimurium VNP20009 in animal-product-free media does not alter schwannoma growth control

Ahmed,

Oliva,

Shao

et al. 2023

Human Vaccines & Immunotherapeutics

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Schwannomas are slow-growing benign peripheral nerve sheath tumors derived from Schwann-lineage cells that develop in association with NF2-related schwannomatosis (NF2) and schwannomatosis (NF3), as well as spontaneously. Individuals affected with NF2 and NF3 have multiple schwannomas with tumors arising throughout life. Surgical resection, the standard management, is limited in scope and efficacy and is itself associated with significant morbidity. We have previously shown that direct intratumoral injection of attenuated Salmonella Typhimurium ( S . Typhimurium), strain VNP20009, showed a potent anti-tumor effect in preclinical NF-2 schwannoma models. The United States Federal Drug Administration (FDA) requires that bacterial products utilized in clinical trials be produced without exposure to animal-derived-products. In this context, we developed, characterized, and tested the antitumor efficacy of an attenuated S . Typhimurium serially passaged in animal-product-free media, naming it VNP20009-AF for “VNP20009-animal-product-free.” Our in vitro data did not indicate any significant changes in the viability, motility, or morphology of VNP20009-AF, compared to its parental strain. In vivo efficacy data demonstrated that VNP20009-AF and VNP20009 controlled tumor growth to the same degree in both human NF2-schwannoma xenograft and murine-NF2 schwannoma allograft models. Together, these data support the use of VNP20009-AF for the translation of bacterial schwannoma therapy into clinical trials.

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“…24,25 This therapy involves the administration of one or several (<5 fractions) high doses of ionizing radiation (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), which often cause complications such as dizziness, damage to adjacent nerves, including the auditory nerve, or malignancy of the lesion. 26,27 For that reason, it is essential to consider a substance that will increase the toxicity of ionizing radiation in tumors and at the same time protect surrounding cells. Due to the fact that CBD exhibits both anti-cancer and neuroprotective effects it may have the potential to fulfill these criteria as a novel adjunct agent for radiation therapy.…”

Section: Introductionmentioning

confidence: 99%

High resolution optical spectroscopy for the evaluation of cannabidiol efficiency as a radiation therapy support of peripheral nervous system tumors

Chrabąszcz,

Pogoda,

Cieżak

et al. 2023

Preprint

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An increasing number of scientific papers discuss the promising therapeutic potential of cannabidiol (CBD) not only for the treatment of cancer, but also for asthma and neurodegenerative disorders. This happens mainly due to its proven anticancer, anti-inflammatory, and antioxidant properties. In the field of cancer research, the use of CBD has already been investigated on malignant tumors of the central nervous system, like gliomas. So far, CBD has not yet been explored in the therapy of peripheral nervous system (PNS) tumors. Peripheral nerves reside outside the central nervous system, therefore peripheral nerve tumors can occur anywhere in the body. When the tumor develops within large blood vessels, spinal nerves or involves more than one peripheral nerve, radiotherapy is recommended. Due to high doses of ionizing radiation, complications such as dizziness, damage to adjacent nerves, or malignancy of the lesion may occur. Therefore, it is important to develop a treatment scheme that efficiently reduces tumor volume while maintaining the normal functions of the surrounding cells and decrease the side effects. Herein, we proposed to combine hyperspectral imaging using Raman and FTIR spectroscopy and AFM-IR technique as a novel approach to monitor the therapeutic efficacy of CBD. Performed studies reviled the dual effect of CBD, that protects normal cells from ionizing radiation and increases its toxicity in cancer cells.

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Transition of a vestibular schwannoma to a malignant peripheral nerve sheath tumor with loss of H3K27 trimethylation after radiosurgery—a case report and review of the literature

Cited by 6 publications

References 51 publications

Epigenetic Regulation in Primary CNS Tumors: An Opportunity to Bridge Old and New WHO Classifications

Epigenetic Regulation in Primary CNS Tumors: An Opportunity to Bridge Old and New WHO Classifications

Culture of attenuated Salmonella Typhimurium VNP20009 in animal-product-free media does not alter schwannoma growth control

High resolution optical spectroscopy for the evaluation of cannabidiol efficiency as a radiation therapy support of peripheral nervous system tumors

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