2024
NAPRT Silencing in FH-Deficient Renal Cell Carcinoma Confers Therapeutic Vulnerabilities via NAD+ Depletion
Noronha K, Lucas K, Paradkar S, Edmonds J, Friedman S, Murray M, Liu S, Sajed D, Sachs C, Spurrier J, Raponi M, Liang J, Zeng H, Sundaram R, Shuch B, Vasquez J, Bindra R. NAPRT Silencing in FH-Deficient Renal Cell Carcinoma Confers Therapeutic Vulnerabilities via NAD+ Depletion. Molecular Cancer Research 2024, 22: of1-of16. PMID: 38949523, PMCID: PMC11445649, DOI: 10.1158/1541-7786.mcr-23-1003.Peer-Reviewed Original ResearchRenal cell carcinomaCellular processesCell carcinomaFumarate hydrataseImpact diverse cellular processesAlpha-ketoglutarate-dependent dioxygenasesDiverse cellular processesAccumulation of fumaratePreiss-Handler pathwayMultiple cellular processesLoss of function mutationsAssociated with silencingNicotinamide phosphoribosyl transferase inhibitorPattern of hypermethylationFH-deficient renal cell carcinomasSynergistic tumor cell killingAggressive subtype of renal cell carcinomaLoss of FHSubtype of renal cell carcinomaDNA repair processesPoly(ADP)-ribose polymerase inhibitorsCpG islandsTumor cell killingPreiss-HandlerCell line models
2020
Oncometabolites suppress DNA repair by disrupting local chromatin signalling
Sulkowski PL, Oeck S, Dow J, Economos NG, Mirfakhraie L, Liu Y, Noronha K, Bao X, Li J, Shuch BM, King MC, Bindra RS, Glazer PM. Oncometabolites suppress DNA repair by disrupting local chromatin signalling. Nature 2020, 582: 586-591. PMID: 32494005, PMCID: PMC7319896, DOI: 10.1038/s41586-020-2363-0.Peer-Reviewed Original ResearchConceptsDNA repairDNA breaksFumarate hydrataseDownstream repair factorsHistone 3 lysine 9Homology-dependent repairPoly (ADP-ribose) polymeraseRecruitment of TIP60Deregulation of metabolismChromatin signalingSuccinate dehydrogenase genesGenome integrityLysine 9Repair factorsDehydrogenase geneEnd resectionIsocitrate dehydrogenase 1Aberrant hypermethylationMechanistic basisSomatic mutationsDehydrogenase 1GenesHuman malignanciesProper executionMutationsEstimation of the carrier frequency of fumarate hydratase alterations and implications for kidney cancer risk in hereditary leiomyomatosis and renal cancer
Shuch B, Li S, Risch H, Bindra RS, McGillivray PD, Gerstein M. Estimation of the carrier frequency of fumarate hydratase alterations and implications for kidney cancer risk in hereditary leiomyomatosis and renal cancer. Cancer 2020, 126: 3657-3666. PMID: 32413184, PMCID: PMC10316675, DOI: 10.1002/cncr.32914.Peer-Reviewed Original ResearchConceptsFumarate hydrataseExome Aggregation ConsortiumAllele frequenciesFH geneGenome ProjectDifferent world populationsFH alterationsHereditary leiomyomatosisKidney cancer riskCancer penetranceMissense alterationsGenesOverall allele frequencyRare variantsLow penetranceRenal cancerExACKidney cancerCancer riskPenetranceGermline mutationsLethal formWorld populationCancer syndromesAlterations
2018
Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair
Sulkowski PL, Sundaram RK, Oeck S, Corso CD, Liu Y, Noorbakhsh S, Niger M, Boeke M, Ueno D, Kalathil AN, Bao X, Li J, Shuch B, Bindra RS, Glazer PM. Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair. Nature Genetics 2018, 50: 1086-1092. PMID: 30013182, PMCID: PMC6072579, DOI: 10.1038/s41588-018-0170-4.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksPGL/PCCDNA repair deficiency syndromeHomologous recombination DNA repair pathwayDNA repair pathwaysDouble-strand breaksHomologous recombination DNA repairSynthetic lethal targetingGenomic integrityDNA repairFumarate hydrataseMechanistic basisCancer predispositionFunction mutationsGermline lossKrebs cycleSuccinate dehydrogenaseHereditary paragangliomaRespectively1–3Ribose polymerase inhibitorsHereditary leiomyomatosisHereditary cancer syndromesCancer syndromesTumor cellsPolymerase inhibitors