Knowledge Graph Triples
Generated: 2026-07-11
Updated: 2026-07-12 (Dahlmann 2009 + Buesco 2020 — 17 new triples, 0 contradictions)
Sources: 39 source summaries (26 produced triples)
Total triples: 186
Format: subject relation object provenance evidence_level
Unresolved entities (no wiki page yet): NRAS, MYC, WT1, APC, SMAD4, ERBB2, MET, STAT6, FOLH1, BRCA1, VHL, SETD2, KDM5C, MTOR, PTEN, ccRCC, Everolimus, crizotinib, nivolumab, DeCiFer, PyClone, lung-adenocarcinoma, lung-squamous-cell-carcinoma, DNA_damage_response, genomic_uracil, UDG_pretreatment, molecular_tagging, duplex_sequencing, macrodissection
clonal_hematopoiesis confounds ctdna asco-gu-2025-ctdna-next-generation verified epigenomic_technologies enhances ctdna asco-gu-2025-ctdna-next-generation verified category-theory provides_formalism_for valid-analogy buehler2011-reoccurring-patterns “Category theory provides formal criteria for valid analogies; commutativity condition distinguishes valid analogies from mere metaphors” commutativity-condition is_formal_criterion_for structure-preserving-mapping buehler2011-reoccurring-patterns “Commutativity condition — if two paths in the source olog point to the same instance, their images in the target olog must also point to the same instance” functorial-analogy is_applied_to cross-domain-knowledge-transfer buehler2011-reoccurring-patterns “Functorial mapping that validates cross-domain knowledge transfer is category theory’s added value over graph theory” driver-mutation affects clone-fitness buehler2011-reoccurring-patterns “Hierarchical interaction captures why driver mutations (lower-level genetic changes) affect clone fitness (higher-level population property)” hierarchical-olog provides_formalism_for cross-domain-analogy buehler2011-reoccurring-patterns “Hierarchical olog captures shared structure as a functorial isomorphism; spider silk and classical music share structurally identical hierarchical architecture” APOBEC3B-deletion associated_with increased-breast-cancer-risk burns2014-apobec3b-pathological-consequences verified_with_caveats APOBEC3B upregulated_in bladder-cancer burns2014-apobec3b-pathological-consequences verified_with_caveats APOBEC3B upregulated_in breast-cancer burns2014-apobec3b-pathological-consequences verified_with_caveats APOBEC3B upregulated_in cervical-cancer burns2014-apobec3b-pathological-consequences verified_with_caveats APOBEC3B upregulated_in head-and-neck-cancer burns2014-apobec3b-pathological-consequences verified_with_caveats APOBEC3B upregulated_in lung-cancer burns2014-apobec3b-pathological-consequences verified_with_caveats ctdna captures intratumor_heterogeneity cfdna-vs-ctdna-explained verified_with_caveats ctdna detects cancer cfdna-vs-ctdna-explained verified_with_caveats ctdna is_subset_of cfdna cfdna-vs-ctdna-explained verified_with_caveats ctdna monitors treatment_response cfdna-vs-ctdna-explained verified_with_caveats biomolecular-condensate is_simultaneously text-and-reader extended-brain-2026-life-is-interpretation “BMC is simultaneously text and reader; carries meaningful configuration and performs the reading; epistemic cut is functional, not physical” biomolecular-condensate combines five-constitutive-properties extended-brain-2026-life-is-interpretation “BMCs combine five mutually constitutive properties: liquid, solid, chemical reactor, signaling hub, computational element; entanglement defeats existing physical theory” write-read-rewrite-loop is_mechanism_of cell-differentiation extended-brain-2026-life-is-interpretation “Cell differentiation proceeds through continuous self-reading and self-modification: eRNAs → condensate nucleation → histone modification → new gene activation → new eRNAs” epistemic-cut is_applied_to biomolecular-condensate extended-brain-2026-life-is-interpretation “Epistemic cut runs through the condensate, not between separate objects; the cut is functional, not physical” interpretation is_organizational_principle_of life extended-brain-2026-life-is-interpretation “Interpretation is the organizational principle of life at every scale: bacterial chemotaxis, immune recognition, plant-insect signaling — same structural logic operates” APC mutated_in colorectal-cancer lee2026-clonal-evolution-crc verified BRCA1 inactivated_by LINE-1-retrotransposition lee2026-clonal-evolution-crc verified chromothripsis occurs_in colorectal-cancer lee2026-clonal-evolution-crc verified ERBB2 amplified_in colorectal-cancer lee2026-clonal-evolution-crc verified KRAS mutated_in colorectal-cancer lee2026-clonal-evolution-crc verified LINE-1-retrotransposition elevated_in colorectal-cancer lee2026-clonal-evolution-crc verified MDM2 amplified_in colorectal-cancer lee2026-clonal-evolution-crc verified MYC amplified_in colorectal-cancer lee2026-clonal-evolution-crc verified NRAS lost_in liver-metastasis lee2026-clonal-evolution-crc verified NRAS mutated_in colorectal-cancer lee2026-clonal-evolution-crc verified RBFOX1 deleted_in colorectal-cancer lee2026-clonal-evolution-crc verified SMAD4 deleted_in colorectal-cancer lee2026-clonal-evolution-crc verified TP53 mutated_in colorectal-cancer lee2026-clonal-evolution-crc verified hierarchical-interaction describes_relation_between higher-level-property lower-level-element buehler2011-reoccurring-patterns “Property of a higher-level structure can relate to an element of a lower-level structure, crossing hierarchical boundaries that usually separate composition levels” chromothripsis occurs_in neuroblastoma ma2018-pediatric-pancancer verified chromothripsis occurs_in osteosarcoma ma2018-pediatric-pancancer verified chromothripsis occurs_in pediatric-AML ma2018-pediatric-pancancer verified chromothripsis occurs_in pediatric-B-ALL ma2018-pediatric-pancancer verified chromothripsis occurs_in Wilms-tumor ma2018-pediatric-pancancer verified KRAS-novel-isoform expressed_in pediatric-leukemia ma2018-pediatric-pancancer verified WT1 epigenetically-silenced_in pediatric-AML ma2018-pediatric-pancancer verified chromothripsis deletes CXCR4-mutant-allele mcdermott2015-chromothriptic-cure-whim verified CXCR4-haploinsufficiency confers_selective_advantage hematopoietic-stem-cell mcdermott2015-chromothriptic-cure-whim verified CXCR4 mutated_in WHIM-syndrome mcdermott2015-chromothriptic-cure-whim verified chromosome-1q-gain occurs_in multiple-myeloma miething2019-clonal-evolution-myeloma verified_with_caveats MYC translocated_in multiple-myeloma miething2019-clonal-evolution-myeloma verified_with_caveats RB1 inactivated_in multiple-myeloma miething2019-clonal-evolution-myeloma verified_with_caveats TP53 inactivated_in multiple-myeloma miething2019-clonal-evolution-myeloma verified_with_caveats ar downregulated_in prostate-cancer mikutenaite2025-clonal-evolution-transcriptional-plasticity verified_with_caveats JAK-STAT_pathway activated_in prostate-cancer mikutenaite2025-clonal-evolution-transcriptional-plasticity verified_with_caveats monophyletic_dissemination occurs_in prostate-cancer mikutenaite2025-clonal-evolution-transcriptional-plasticity verified_with_caveats polyphyletic_dissemination occurs_in prostate-cancer mikutenaite2025-clonal-evolution-transcriptional-plasticity verified_with_caveats single_biopsy underestimates intratumor_heterogeneity mikutenaite2025-clonal-evolution-transcriptional-plasticity verified_with_caveats transcriptional_plasticity associated_with metastasis mikutenaite2025-clonal-evolution-transcriptional-plasticity verified_with_caveats WNT_pathway activated_in prostate-cancer mikutenaite2025-clonal-evolution-transcriptional-plasticity verified_with_caveats DCF reclassifies SNV_clonality satas2022-decifer verified_with_caveats DeCiFer outperforms PyClone satas2022-decifer verified_with_caveats DeCiFer resolves homoplasy satas2022-decifer verified_with_caveats SSCN_assumption improves_upon constant_mutation_multiplicity_assumption satas2022-decifer verified_with_caveats chemotherapy preserves ancestral_clones spina2018-ctdna-hodgkin-lymphoma verified ctdna detects Hodgkin_lymphoma spina2018-ctdna-hodgkin-lymphoma verified ctdna genotypes Hodgkin_lymphoma spina2018-ctdna-hodgkin-lymphoma verified ctdna predicts treatment_response spina2018-ctdna-hodgkin-lymphoma verified ITPKB mutated_in Hodgkin_lymphoma spina2018-ctdna-hodgkin-lymphoma verified nivolumab suppresses ancestral_clones spina2018-ctdna-hodgkin-lymphoma verified STAT6 mutated_in Hodgkin_lymphoma spina2018-ctdna-hodgkin-lymphoma verified TNFAIP3 mutated_in Hodgkin_lymphoma spina2018-ctdna-hodgkin-lymphoma verified cfdna released_by apoptosis stejskal2023-ctdna-biology-review verified ctdna assesses intratumor_heterogeneity stejskal2023-ctdna-biology-review verified ctdna has_half_life short stejskal2023-ctdna-biology-review verified ctdna measured_in cfdna stejskal2023-ctdna-biology-review verified ctRNA released_by active_secretion stejskal2023-ctdna-biology-review verified clonal_diversity decreases_in breast-cancer walens2020-adaptation-selection-clonal-evolution verified_with_caveats crizotinib treats breast-cancer walens2020-adaptation-selection-clonal-evolution verified_with_caveats EMT occurs_in breast-cancer walens2020-adaptation-selection-clonal-evolution verified_with_caveats IL-6-Jak-Stat3_pathway activated_in breast-cancer walens2020-adaptation-selection-clonal-evolution verified_with_caveats Jak_inhibitor treats breast-cancer walens2020-adaptation-selection-clonal-evolution verified_with_caveats MET amplified_in breast-cancer walens2020-adaptation-selection-clonal-evolution verified_with_caveats CDK4/6i+ET-R associated_with worse_outcome wander2026-ctdna-cdk46-breast-cancer verified_with_caveats ctdna associated_with prognosis wander2026-ctdna-cdk46-breast-cancer verified_with_caveats esr1 enriched_in breast-cancer wander2026-ctdna-cdk46-breast-cancer verified_with_caveats esr1 under_selection_in breast-cancer wander2026-ctdna-cdk46-breast-cancer verified_with_caveats rb1 enriched_in breast-cancer wander2026-ctdna-cdk46-breast-cancer verified_with_caveats rb1 under_selection_in breast-cancer wander2026-ctdna-cdk46-breast-cancer verified_with_caveats tp53 under_selection_in breast-cancer wander2026-ctdna-cdk46-breast-cancer verified_with_caveats clonal_evolution generates transcriptional_noise weng2026-ith-prostate-cancer verified_with_caveats FOLH1 expression_driven_by transcriptional_plasticity weng2026-ith-prostate-cancer verified_with_caveats transcriptional_ITH independent_of clonal_evolution weng2026-ith-prostate-cancer verified_with_caveats transcriptional_ITH occurs_in prostate-cancer weng2026-ith-prostate-cancer verified_with_caveats tumor_microenvironment limited_role_in transcriptional_ITH weng2026-ith-prostate-cancer verified_with_caveats VHL mutated_in ccRCC Entities Referenced ubiquitously mutated (2-bp deletion) in Patient 1 VHL located_on chromosome 3p Entities Referenced on chromosome 3p SETD2 inactivated_in ccRCC Key Findings harbored three distinct inactivating mutations with different spatial distributions SETD2 demonstrates convergent evolution Key Findings three distinct inactivating mutations all on background of ubiquitous 3p loss of heterozygosity (deleting the other SETD2 allele) KDM5C inactivated_in ccRCC Key Findings two distinct disruptive mutations KDM5C demonstrates convergent evolution Key Findings two distinct disruptive mutations confirmed by immunohistochemistry showing reduced H3K4 trimethylation MTOR mutated_in ccRCC Key Findings L2431P kinase-domain mutation present in all primary tumor regions except R4 MTOR L2431P produces constitutive mTOR activation Key Findings increased phospho-S6 and phospho-4EBP staining; transfection experiments confirmed L2431P promotes constitutive mTOR activation PTEN inactivated_in ccRCC Entities Referenced multiple distinct inactivating mutations within a single tumor Everolimus targets MTOR Entities Referenced mTOR inhibitor used in E-PREDICT trial ccRCC demonstrates intratumor-heterogeneity Core Argument spatially separated regions of the same tumor harbor distinct mutations, chromosomal aberrations, and prognostic gene-expression signatures ccRCC demonstrates branching-evolution Core Argument tumors evolve through branched rather than linear evolutionary trajectories; branching phylogenetic tree revealed by clonal ordering of 128 mutations Multiregion sequencing detects intratumor-heterogeneity Methods exome sequencing of 4 patients; for Patient 1: 9 primary-tumor regions, 2 pretreatment biopsies, 2 metastatic regions Single biopsy underrepresents mutational landscape Key Findings a single biopsy reveals only ~55% of all mutations detected across all regions; only 34% of mutations were ubiquitous Intratumor heterogeneity pre-exists therapy Key Findings pretreatment samples shared 67 of 71 mutations with post-treatment primary tumor regions; main phylogenetic branches present before everolimus exposure Intratumor heterogeneity challenges therapy-resistance Relevance to Clonal Evolution if the target mutation is present in only a subset of regions, targeted therapy will leave untargeted clones to progress Branching evolution challenges linear clonal succession Relevance to Clonal Evolution before Gerlinger 2012, the dominant model was linear clonal succession (Nowell 1976) Convergent evolution produces phenotypic homogeneity Relevance to Clonal Evolution different mutations produce the same functional outcome; strong evidence for Darwinian selection acting on phenotypes, not genotypes Convergent evolution detected_by intratumor-heterogeneity Concepts Introduced or Used independent acquisition of distinct mutations that produce the same phenotypic outcome (e.g., loss of SETD2 function through three different mutations); detectable only when ITH is resolved Gerlinger2012 introduces multiregion sequencing Core Argument the paper introduced multi-region sequencing as a methodology enabling detection of ITH that single-biopsy approaches miss Gerlinger2012 demonstrates branching-evolution Key Findings clonal ordering of 128 mutations from Patient 1 revealed a branching phylogenetic tree: one branch to metastatic clones, the other diversified into primary-tumor regions Gerlinger2012 demonstrates convergent evolution Key Findings SETD2 (three distinct inactivating mutations) and KDM5C (two distinct disruptive mutations) each acquired distinct mutations converging on same functional loss Gerlinger2012 provides foundation for ctDNA monitoring Relevance to Clonal Evolution finding that single biopsy captures only ~55% of mutations motivated the entire field of ctDNA-based non-invasive multi-clone monitoring APOBEC3B localizes_to nucleus burns2013-apobec3b-breast-cancer unverified APOBEC3B generates C-to-U_deamination burns2013-apobec3b-breast-cancer unverified APOBEC3B prefers TC_dinucleotide_context burns2013-apobec3b-breast-cancer unverified APOBEC3B_expression correlates_with C-to-T_mutation_load burns2013-apobec3b-breast-cancer unverified APOBEC3B_expression correlates_with total_mutation_load burns2013-apobec3b-breast-cancer unverified APOBEC3B generates genomic_uracil burns2013-apobec3b-breast-cancer unverified APOBEC3B contributes_to tumor_heterogeneity burns2013-apobec3b-breast-cancer unverified APOBEC3B_overexpression causes DNA_damage_response burns2013-apobec3b-breast-cancer unverified TP53_inactivation correlates_with APOBEC3B_expression burns2013-apobec3b-breast-cancer unverified APOBEC3B_mutagenesis contributes_to clonal_evolution burns2013-apobec3b-breast-cancer unverified APOBEC3B proposed_as therapeutic_target burns2013-apobec3b-breast-cancer unverified APOBEC3B upregulated_in lung-adenocarcinoma burns2013-apobec3b-multiple-cancers unverified APOBEC3B upregulated_in lung-squamous-cell-carcinoma burns2013-apobec3b-multiple-cancers unverified APOBEC3B_expression correlates_with C/G_mutation_bias burns2013-apobec3b-multiple-cancers unverified APOBEC3B_expression correlates_with mutation_load burns2013-apobec3b-multiple-cancers unverified APOBEC3B_expression correlates_with kataegis_frequency burns2013-apobec3b-multiple-cancers unverified APOBEC3B_signature matches recombinant_APOBEC3B_signature burns2013-apobec3b-multiple-cancers unverified kataegis associated_with APOBEC3B_expression burns2013-apobec3b-multiple-cancers unverified APOBEC3B_mutagenesis generates kataegis burns2013-apobec3b-multiple-cancers unverified APOBEC3B_mutagenesis active_in multiple_cancer_types burns2013-apobec3b-multiple-cancers unverified six_cancer_types converge_on APOBEC3B_mutagenesis burns2013-apobec3b-multiple-cancers unverified FFPE_fixation introduces C>T_artifacts do2015-sequence-artifacts-ffpe unverified cytosine_deamination generates uracil_lesions do2015-sequence-artifacts-ffpe unverified uracil_lesions cause C:G>T:A_transitions do2015-sequence-artifacts-ffpe unverified 5-methylcytosine_deamination generates thymine_lesions do2015-sequence-artifacts-ffpe unverified UDG_pretreatment reduces C>T_artifacts do2015-sequence-artifacts-ffpe unverified UDG_pretreatment does_not_remove 5-mC_deamination_artifacts do2015-sequence-artifacts-ffpe unverified molecular_tagging distinguishes true_mutations_from_artifacts do2015-sequence-artifacts-ffpe unverified duplex_sequencing achieves 1:10000_sensitivity do2015-sequence-artifacts-ffpe unverified FFPE_artifacts mimic actionable_mutations do2015-sequence-artifacts-ffpe unverified EGFR_T790M falsely_detected_in FFPE_lung_tumors do2015-sequence-artifacts-ffpe unverified KRAS_codon12/13 falsely_detected_in FFPE_colorectal_cancer do2015-sequence-artifacts-ffpe unverified FFPE_fixation degrades DNA greytak2015-ffpe-biospecimen-accuracy unverified FFPE_fixation degrades RNA greytak2015-ffpe-biospecimen-accuracy unverified FFPE_fixation preserves protein zhu2019-ffpe-proteomics-pct-swath unverified FFPE_vs_frozen genotype_concordance 59-99_percent greytak2015-ffpe-biospecimen-accuracy unverified FFPE_vs_frozen CNA_concordance 53-98_percent greytak2015-ffpe-biospecimen-accuracy unverified FFPE_vs_frozen DEG_overlap 33_percent greytak2015-ffpe-biospecimen-accuracy unverified FFPE_false_positive_SNV_rate range 1-15_percent greytak2015-ffpe-biospecimen-accuracy unverified diagnosis interacts_with preservation_method greytak2015-ffpe-biospecimen-accuracy unverified FFPE_GC_content affects genotype_concordance greytak2015-ffpe-biospecimen-accuracy unverified FFPE_proteome comparable_to FF_proteome zhu2019-ffpe-proteomics-pct-swath unverified FFPE_proteome temporally_stable 1-15_years zhu2019-ffpe-proteomics-pct-swath unverified FFPE_proteomics superior_to FF_proteomics zhu2019-ffpe-proteomics-pct-swath unverified FFPE_artifact_spectrum includes C>A_G>T_oxidation steiert2023-ffpe-dna-ngs-paradigms unverified FFPE_artifacts AAF_exceeds 10_percent steiert2023-ffpe-dna-ngs-paradigms unverified FFPE_artifacts penetrate 5_percent_VAF_filter steiert2023-ffpe-dna-ngs-paradigms unverified FFPE_duplication_ratio 2x_higher_than FF steiert2023-ffpe-dna-ngs-paradigms unverified FFPE_insert_sizes half_of FF steiert2023-ffpe-dna-ngs-paradigms unverified FFPE_coverage_uniformity lower_than FF steiert2023-ffpe-dna-ngs-paradigms unverified AT-rich_regions systematic_dropout_in FFPE steiert2023-ffpe-dna-ngs-paradigms unverified FFPE_library_prep input_requirements vary_20-fold pignatta2025-ffpe-rnaseq-library-prep unverified macrodissection required_for FFPE_RNA-seq pignatta2025-ffpe-rnaseq-library-prep unverified abasic_site formation_rate 10000_per_genome_per_day dahlmann2009-biochemical-dna-damage unverified depurination rate 3e-11_per_second dahlmann2009-biochemical-dna-damage unverified depyrimidination rate 20x_slower_than_depurination dahlmann2009-biochemical-dna-damage unverified abasic_site destabilizes_duplex 3-11_kcal_per_mol dahlmann2009-biochemical-dna-damage unverified A-rule governs polymerase_insertion_at_abasic_sites dahlmann2009-biochemical-dna-damage unverified DNA_polymerase inserts adenine_opposite_abasic_site dahlmann2009-biochemical-dna-damage unverified 2-deoxyribonolactone templates thymine_not_adenine dahlmann2009-biochemical-dna-damage unverified methoxyamine blocks AP_endonuclease dahlmann2009-biochemical-dna-damage unverified oxidative_damage dominates FFPE_artifacts buesco2020-ffpe-bacterial-dna-damage unverified FFPE_bacterial_DNA highly_fragmented relative_to_fresh buesco2020-ffpe-bacterial-dna-damage unverified FFPE_bacterial_DNA poor_template_for PCR buesco2020-ffpe-bacterial-dna-damage unverified heat_decrosslinking generates ss-breaks_and_chimeras buesco2020-ffpe-bacterial-dna-damage unverified low-temperature_decrosslinking reduces heat_induced_artifacts buesco2020-ffpe-bacterial-dna-damage unverified BER_reconstitution repairs oxidative_lesions buesco2020-ffpe-bacterial-dna-damage unverified BER_reconstitution improves FFPE_sequencing_quality buesco2020-ffpe-bacterial-dna-damage unverified UDG_alone insufficient_for FFPE_repair buesco2020-ffpe-bacterial-dna-damage unverified BER_reconstitution effective_on bacterial_and_mammalian_FFPE_DNA buesco2020-ffpe-bacterial-dna-damage unverified