Germline loss-of-function variant in the E3 ubiquitin ligase TRAF2 in a young adult patient with medulloblastoma: a case report.

Publisher: BioMed Central Country of Publication: England NLM ID: 101610673 Publication Model: Electronic Cited Medium: Internet ISSN: 2051-5960 (Electronic) Linking ISSN: 20515960 NLM ISO Abbreviation: Acta Neuropathol Commun Subsets: MEDLINE

Original Publication: London : BioMed Central, [2013]-

Medulloblastoma*/genetics ; Medulloblastoma*/pathology ; Germ-Line Mutation* ; TNF Receptor-Associated Factor 2*/genetics ; TNF Receptor-Associated Factor 2*/metabolism ; Cerebellar Neoplasms*/genetics ; Cerebellar Neoplasms*/pathology; Humans ; Young Adult ; Male ; Loss of Function Mutation ; Adult ; Female

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.
Competing Interests: Declarations. Ethics approval and consent to participate: All samples were acquired after patients provided written informed consent in compliance with the University of Michigan Institutional Review Board. Patient consent: The investigators have obtained consent to publish the data and images contained within the following case report. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)

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U2CCA271854-03 Early Detection Research Network; U2CCA271854-03 Early Detection Research Network; CSDG-21-177-01 American Cancer Society; R35CA231996 NCI Outstanding Investigator Award

Keywords: TRAF2; AYA; Genetic tumor syndromes; Medulloblastoma

0 (TNF Receptor-Associated Factor 2)

Date Created: 20241221 Date Completed: 20241221 Latest Revision: 20241221

20241222

10.1186/s40478-024-01896-8

39707575