{"id":"1041488d-f18d-5717-888f-e040804091ec","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:tet2-mutation-lowers-marrow-5hmc","predicate":"loss_reduces","statement":"Bone marrow from patients carrying TET2 mutations showed uniformly low 5-hydroxymethylcytosine in genomic DNA compared with bone marrow from healthy controls, and the mutations compromised catalytic activity in the same study.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"4dbffa16-3dee-57a1-b672-91f3758a668a","mechanism_event_label":"Bone marrow from patients carrying TET2 mutations showed uniformly low 5-hydroxymethylcytosine in genomic DNA compared with bone marrow from healthy controls, and the mutations compromised catalytic activity in the same study.","subject":{"id":"5433ea92-f679-5b25-a872-cb8a636ae4e1","slug":"tet2-human","display_name":"Human TET2","entity_type_key":"protein"},"object":{"id":"507c6ac8-bf1a-5662-811c-ac813737015e","slug":"human-bone-marrow-5hmc","display_name":"Bone-marrow genomic 5-hydroxymethylcytosine content","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"4dbffa16-3dee-57a1-b672-91f3758a668a","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:tet2-mutation-lowers-marrow-5hmc-event","event_type":"observed_relationship","label":"Bone marrow from patients carrying TET2 mutations showed uniformly low 5-hydroxymethylcytosine in genomic DNA compared with bone marrow from healthy controls, and the mutations compromised catalytic activity in the same study.","description":"Patients with a damaged TET2 had less of the chemical mark the enzyme makes.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"5433ea92-f679-5b25-a872-cb8a636ae4e1","slug":"tet2-human","display_name":"Human TET2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"507c6ac8-bf1a-5662-811c-ac813737015e","slug":"human-bone-marrow-5hmc","display_name":"Bone-marrow genomic 5-hydroxymethylcytosine content","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"duration","value_text":"Cross-sectional","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Patient bone-marrow samples with and without TET2 mutations; catalytic assays of mutant protein","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"No intervention; naturally occurring mutations","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Samples with low 5hmC showed hypomethylation relative to controls at the majority of differentially methylated CpG sites, so the downstream methylation consequence is not a simple global gain.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Patients with a damaged TET2 had less of the chemical mark the enzyme makes.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ko-2010] Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2 (2010). https://pubmed.ncbi.nlm.nih.gov/21057493/ DOI: 10.1038/nature09586","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Bone marrow genomic DNA","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"d16ce4e6-9efb-59f9-b436-7e0f50b9492a","evidence_kind":"source_excerpt","locator":"Lines 33-41","start_line":33,"end_line":41,"excerpt":"## tet2-mutation-lowers-marrow-5hmc\nBone marrow from patients carrying TET2 mutations showed uniformly low 5-hydroxymethylcytosine in genomic DNA compared with bone marrow from healthy controls, and the mutations compromised catalytic activity in the same study.\nModel/species: Patient bone-marrow samples with and without TET2 mutations; catalytic assays of mutant protein\nOrganism: Homo sapiens\nTissue/system: Bone marrow genomic DNA\nExposure: No intervention; naturally occurring mutations\nDuration: Cross-sectional\nLimits: Samples with low 5hmC showed hypomethylation relative to controls at the majority of differentially methylated CpG sites, so the downstream methylation consequence is not a simple global gain.\nPrimary reference: [ko-2010] Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2 (2010). https://pubmed.ncbi.nlm.nih.gov/21057493/ DOI: 10.1038/nature09586","model_system":"Patient bone-marrow samples with and without TET2 mutations; catalytic assays of mutant protein","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c0b9b176-985b-55c7-b8f5-f3ca16a7ddfe","stable_key":"import-a2968a2f-5b00-5212-8b8c-8a4262bcb149","title":"TET2 loss and malignancy: the step between a nutrient-responsive enzyme and the disease (2026-09-23)","document_type":"imported_text","citation_label":"Original AI-assisted curation of twelve primary studies located by Europe PMC title search, with every statement drafted from the retrieved abstract. Two pairs share a laboratory and are recorded as one line of evidence each. Genetic loss of function, pharmacological exposure and dietary depletion are kept as separate record types. Not publisher full text.","file_path":"","sha256":"22e2c8388d4f0c1813546ba6a9ccee3fa14c0c8f578bd9bd80103c1390b2536b","revision_id":"fbc29d8d-0420-562c-bfdb-1b5af42f2d08","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}