Vo Josh N, Franson Andrea, Waszak Sebastian M, Wu Yi-Mi, Becker Nicole, Chinnaiyan Arul M, Robinson Dan R
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Acta Neuropathol Commun. 2024 Dec 20;12(1):195. doi: 10.1186/s40478-024-01896-8.
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.
我们在一名被诊断为髓母细胞瘤的年轻成年患者中，鉴定出肿瘤坏死因子受体相关因子2（TRAF2）中一种罕见的杂合性种系功能丧失变异。该变异位于E3泛素连接酶蛋白的TRAF-C结构域内，预计会降低TRAF2与上游受体及相关衔接蛋白的结合亲和力。整合基因组学显示，在髓母细胞瘤基因组中，通过9号染色体q臂的部分拷贝中性杂合性丧失，导致TRAF2双等位基因缺失。我们进一步对使用相同平台测序的20例髓母细胞瘤内部队列进行了比较分析，揭示了与TRAF2相关的髓母细胞瘤的非典型分子特征。我们的研究增加了不断扩大的遗传性肿瘤综合征目录，这些综合征会增加携带者患髓母细胞瘤的易感性。
