Germline loss-of-function variant in the E3 ubiquitin ligase TRAF2 in a young adult patient with medulloblastoma: a case report
Abstract We identified a rare heterozygous germline loss-of-function variant in the tumor necrosis factor receptor-associated factor 2 (TRAF2) in a young adult patient diagnosed with medulloblastoma. This variant is located within the TRAF-C domain of the E3 ubiquitin ligase protein and is predicted...
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| Format: | Article |
| Language: | English |
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BMC
2024-12-01
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| Series: | Acta Neuropathologica Communications |
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| Online Access: | https://doi.org/10.1186/s40478-024-01896-8 |
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| author | Josh N. Vo Andrea Franson Sebastian M. Waszak Yi-Mi Wu Nicole Becker Arul M. Chinnaiyan Dan R. Robinson |
| author_facet | Josh N. Vo Andrea Franson Sebastian M. Waszak Yi-Mi Wu Nicole Becker Arul M. Chinnaiyan Dan R. Robinson |
| author_sort | Josh N. Vo |
| collection | DOAJ |
| description | Abstract We identified a rare heterozygous germline loss-of-function variant in the tumor necrosis factor receptor-associated factor 2 (TRAF2) in a young adult patient diagnosed with medulloblastoma. This variant is located within the TRAF-C domain of the E3 ubiquitin ligase protein and is predicted to diminish the binding affinity of TRAF2 to upstream receptors and associated adaptor proteins. Integrative genomics revealed a biallelic loss of TRAF2 via partial copy-neutral loss-of-heterozygosity of 9q in the medulloblastoma genome. We further performed comparative analysis with an in-house cohort of 20 medulloblastomas sequenced using the same platform, revealing an atypical molecular profile of the TRAF2-associated medulloblastoma. Our research adds to the expanding catalog of genetic tumor syndromes that increase the susceptibility of carriers to MB. |
| format | Article |
| id | doaj-art-c4abc1f3a3df41daa63f20410e78938a |
| institution | OA Journals |
| issn | 2051-5960 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj-art-c4abc1f3a3df41daa63f20410e78938a2025-08-20T01:57:14ZengBMCActa Neuropathologica Communications2051-59602024-12-0112111010.1186/s40478-024-01896-8Germline loss-of-function variant in the E3 ubiquitin ligase TRAF2 in a young adult patient with medulloblastoma: a case reportJosh N. Vo0Andrea Franson1Sebastian M. Waszak2Yi-Mi Wu3Nicole Becker4Arul M. Chinnaiyan5Dan R. Robinson6Michigan Center for Translational Pathology, University of MichiganDepartment of Pediatrics, University of MichiganSchool of Life Sciences, École Polytechnique Fédérale de LausanneMichigan Center for Translational Pathology, University of MichiganDepartment of Pathology, University of MichiganMichigan Center for Translational Pathology, University of MichiganMichigan Center for Translational Pathology, University of MichiganAbstract We identified a rare heterozygous germline loss-of-function variant in the tumor necrosis factor receptor-associated factor 2 (TRAF2) in a young adult patient diagnosed with medulloblastoma. This variant is located within the TRAF-C domain of the E3 ubiquitin ligase protein and is predicted to diminish the binding affinity of TRAF2 to upstream receptors and associated adaptor proteins. Integrative genomics revealed a biallelic loss of TRAF2 via partial copy-neutral loss-of-heterozygosity of 9q in the medulloblastoma genome. We further performed comparative analysis with an in-house cohort of 20 medulloblastomas sequenced using the same platform, revealing an atypical molecular profile of the TRAF2-associated medulloblastoma. Our research adds to the expanding catalog of genetic tumor syndromes that increase the susceptibility of carriers to MB.https://doi.org/10.1186/s40478-024-01896-8MedulloblastomaAYATRAF2Genetic tumor syndromes |
| spellingShingle | Josh N. Vo Andrea Franson Sebastian M. Waszak Yi-Mi Wu Nicole Becker Arul M. Chinnaiyan Dan R. Robinson Germline loss-of-function variant in the E3 ubiquitin ligase TRAF2 in a young adult patient with medulloblastoma: a case report Acta Neuropathologica Communications Medulloblastoma AYA TRAF2 Genetic tumor syndromes |
| title | Germline loss-of-function variant in the E3 ubiquitin ligase TRAF2 in a young adult patient with medulloblastoma: a case report |
| title_full | Germline loss-of-function variant in the E3 ubiquitin ligase TRAF2 in a young adult patient with medulloblastoma: a case report |
| title_fullStr | Germline loss-of-function variant in the E3 ubiquitin ligase TRAF2 in a young adult patient with medulloblastoma: a case report |
| title_full_unstemmed | Germline loss-of-function variant in the E3 ubiquitin ligase TRAF2 in a young adult patient with medulloblastoma: a case report |
| title_short | Germline loss-of-function variant in the E3 ubiquitin ligase TRAF2 in a young adult patient with medulloblastoma: a case report |
| title_sort | germline loss of function variant in the e3 ubiquitin ligase traf2 in a young adult patient with medulloblastoma a case report |
| topic | Medulloblastoma AYA TRAF2 Genetic tumor syndromes |
| url | https://doi.org/10.1186/s40478-024-01896-8 |
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