TOX
Overview
TOX (Thymocyte Selection-Associated High Mobility Group Box) is a transcription factor critical for T-cell and NK-cell development, as well as B-cell biology. In primary central nervous system lymphoma (PCNSL), homozygous and monoallelic deletions of TOX at chromosome 8q12 were identified as novel PCNSL-specific findings not observed in nodal DLBCL.
Alterations observed in the corpus
- Homozygous deletion in 11% and focal monoallelic deletion in 17% of PCNSL cases (N=18 aCGH); novel PCNSL-specific finding not recurrently mutated in nodal DLBCL; loss tentatively associated with shorter overall survival. PMID:25991819
Cancer types (linked)
- PCNSL: Homozygous deletion at 8q12 in 11% (2/18), monoallelic deletion in 17% (3/18); tentatively associated with shorter OS in univariate analysis (requires validation given small N). PMID:25991819
Co-occurrence and mutual exclusivity
- Not recurrently mutated in nodal DLBCL — suggests PCNSL-specific biology. PMID:25991819
Therapeutic relevance
- No direct therapeutic targeting established. TOX is a regulator of T-cell exhaustion; its role in B-cell lymphoma and immune evasion in the CNS compartment is speculative.
Open questions
- Functional role of TOX loss in PCNSL pathogenesis is not validated; no functional experiments in PCNSL models are reported. Prognostic association requires confirmation in larger cohorts. PMID:25991819
Sources
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