A novel case of glial transdifferentiation in renal medullary carcinoma brain metastasis
Abstract Renal medullary carcinoma is a rare undifferentiated tumor of the kidney associated with sickle cell trait and characterized by INI1 (SMARCB1) loss. Although metastasis to lungs, lymph nodes, and bone is commonly reported, distant spread to the central nervous system almost never occurs. He...
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2025-01-01
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| Series: | Acta Neuropathologica Communications |
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| Online Access: | https://doi.org/10.1186/s40478-025-01929-w |
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| author | Maria A. Gubbiotti Ian E. McCutcheon Priya Rao Giannicola Genovese Linghua Wang Artem Tarasov Vladislav Putintsev Amber Berlinski Danil Stupichev Kirill Kriukov Suren Davitavyan Basim Salem Alexander Sarachakov Dmitry Lebedev Michael Hensley Alexander Bagaev Francesca Paradiso Vladimir Kushnarev Gleb Khegai Nizar M. Tannir Pavlos Msaouel |
| author_facet | Maria A. Gubbiotti Ian E. McCutcheon Priya Rao Giannicola Genovese Linghua Wang Artem Tarasov Vladislav Putintsev Amber Berlinski Danil Stupichev Kirill Kriukov Suren Davitavyan Basim Salem Alexander Sarachakov Dmitry Lebedev Michael Hensley Alexander Bagaev Francesca Paradiso Vladimir Kushnarev Gleb Khegai Nizar M. Tannir Pavlos Msaouel |
| author_sort | Maria A. Gubbiotti |
| collection | DOAJ |
| description | Abstract Renal medullary carcinoma is a rare undifferentiated tumor of the kidney associated with sickle cell trait and characterized by INI1 (SMARCB1) loss. Although metastasis to lungs, lymph nodes, and bone is commonly reported, distant spread to the central nervous system almost never occurs. Here we present an unusual case of a patient with renal medullary carcinoma with metastasis to the brain following treatment which included tazemetostat, an EZH2 inhibitor. The metastatic brain lesion harbored morphologic, immunohistochemical, and methylation profile supportive of a primary CNS phenotype with loss of the trimethylated lysine 27 residue of histone 3 while maintaining INI1 loss and a specific gene fusion shared with the patient’s tumor prior to initiation of tazemetostat therapy. Therefore, given the common genetic signatures in the brain metastasis and the patient’s prior tumor, this case represents a rare event of glial transdifferentiation in a brain metastasis of renal medullary carcinoma following the use of an epigenetic modulator. As renal medullary carcinoma has been known to cleverly utilize adaptive mechanisms for survival, we propose that such cell plasticity seen in this case may have been provoked by the use of a drug that alters the epigenetic signature of the tumor cells. Thus, careful assessment of tumor biology following novel therapeutic treatment options must be performed in order to note such unexpected consequences of treatment. |
| format | Article |
| id | doaj-art-82d535febeea4e3fb420856afe55a3e9 |
| institution | Kabale University |
| issn | 2051-5960 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj-art-82d535febeea4e3fb420856afe55a3e92025-01-26T12:57:20ZengBMCActa Neuropathologica Communications2051-59602025-01-0113111110.1186/s40478-025-01929-wA novel case of glial transdifferentiation in renal medullary carcinoma brain metastasisMaria A. Gubbiotti0Ian E. McCutcheon1Priya Rao2Giannicola Genovese3Linghua Wang4Artem Tarasov5Vladislav Putintsev6Amber Berlinski7Danil Stupichev8Kirill Kriukov9Suren Davitavyan10Basim Salem11Alexander Sarachakov12Dmitry Lebedev13Michael Hensley14Alexander Bagaev15Francesca Paradiso16Vladimir Kushnarev17Gleb Khegai18Nizar M. Tannir19Pavlos Msaouel20Department of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Neurosurgery, University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center Unit 1374Department of Genomic Medicine, The University of Texas MD Anderson Cancer CenterBostonGene CorporationBostonGene CorporationBostonGene CorporationBostonGene CorporationBostonGene CorporationBostonGene CorporationBostonGene CorporationBostonGene CorporationBostonGene CorporationBostonGene CorporationBostonGene CorporationBostonGene CorporationBostonGene CorporationBostonGene CorporationDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center Unit 1374Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center Unit 1374Abstract Renal medullary carcinoma is a rare undifferentiated tumor of the kidney associated with sickle cell trait and characterized by INI1 (SMARCB1) loss. Although metastasis to lungs, lymph nodes, and bone is commonly reported, distant spread to the central nervous system almost never occurs. Here we present an unusual case of a patient with renal medullary carcinoma with metastasis to the brain following treatment which included tazemetostat, an EZH2 inhibitor. The metastatic brain lesion harbored morphologic, immunohistochemical, and methylation profile supportive of a primary CNS phenotype with loss of the trimethylated lysine 27 residue of histone 3 while maintaining INI1 loss and a specific gene fusion shared with the patient’s tumor prior to initiation of tazemetostat therapy. Therefore, given the common genetic signatures in the brain metastasis and the patient’s prior tumor, this case represents a rare event of glial transdifferentiation in a brain metastasis of renal medullary carcinoma following the use of an epigenetic modulator. As renal medullary carcinoma has been known to cleverly utilize adaptive mechanisms for survival, we propose that such cell plasticity seen in this case may have been provoked by the use of a drug that alters the epigenetic signature of the tumor cells. Thus, careful assessment of tumor biology following novel therapeutic treatment options must be performed in order to note such unexpected consequences of treatment.https://doi.org/10.1186/s40478-025-01929-wRenal medullary carcinomaINI1SMARCB1Glial transdifferentiationTazemetostatEZH2 |
| spellingShingle | Maria A. Gubbiotti Ian E. McCutcheon Priya Rao Giannicola Genovese Linghua Wang Artem Tarasov Vladislav Putintsev Amber Berlinski Danil Stupichev Kirill Kriukov Suren Davitavyan Basim Salem Alexander Sarachakov Dmitry Lebedev Michael Hensley Alexander Bagaev Francesca Paradiso Vladimir Kushnarev Gleb Khegai Nizar M. Tannir Pavlos Msaouel A novel case of glial transdifferentiation in renal medullary carcinoma brain metastasis Acta Neuropathologica Communications Renal medullary carcinoma INI1 SMARCB1 Glial transdifferentiation Tazemetostat EZH2 |
| title | A novel case of glial transdifferentiation in renal medullary carcinoma brain metastasis |
| title_full | A novel case of glial transdifferentiation in renal medullary carcinoma brain metastasis |
| title_fullStr | A novel case of glial transdifferentiation in renal medullary carcinoma brain metastasis |
| title_full_unstemmed | A novel case of glial transdifferentiation in renal medullary carcinoma brain metastasis |
| title_short | A novel case of glial transdifferentiation in renal medullary carcinoma brain metastasis |
| title_sort | novel case of glial transdifferentiation in renal medullary carcinoma brain metastasis |
| topic | Renal medullary carcinoma INI1 SMARCB1 Glial transdifferentiation Tazemetostat EZH2 |
| url | https://doi.org/10.1186/s40478-025-01929-w |
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