2025
Cancer hotspot mutations rewire ERK2 specificity by selective exclusion of docking interactions
Torres Robles J, Stiegler A, Boggon T, Turk B. Cancer hotspot mutations rewire ERK2 specificity by selective exclusion of docking interactions. Journal Of Biological Chemistry 2025, 301: 108348. PMID: 40015635, DOI: 10.1016/j.jbc.2025.108348.Peer-Reviewed Original ResearchShort linear motifsCancer hotspot mutationsLinear motifsERK substratesYeast two-hybrid libraryHotspot mutationsTwo-hybrid libraryCancer-associated mutantsDocking interactionsWild-type ERK2Cancer-associated mutationsDocking motifBinding sequenceKinase ERK2Co-crystal structureMutant formsERK2 mutantsDisordered regionsERK2MotifStructural rationalePeptide bindingMutationsWT kinasePeptide fragments
2023
Genomics of ERBB2-Positive Breast Cancer in Young Women Before and After Exposure to Chemotherapy Plus Trastuzumab
Lipsyc-Sharf M, Jain E, Collins L, Rosenberg S, Ruddy K, Tamimi R, Schapira L, Come S, Peppercorn J, Borges V, Warner E, Snow C, Krop I, Kim D, Weiss J, Zanudo J, Partridge A, Wagle N, Waks A. Genomics of ERBB2-Positive Breast Cancer in Young Women Before and After Exposure to Chemotherapy Plus Trastuzumab. JCO Precision Oncology 2023, 7: e2300076. PMID: 37364233, DOI: 10.1200/po.23.00076.Peer-Reviewed Original ResearchConceptsPositive breast cancerWhole-exome sequencingBreast cancerYoung womenWomen age 40 yearsErbB2-positive breast cancerErb-b2 receptor tyrosine kinase 2Half of patientsTime pointsLarge prospective cohortAge 40 yearsPost-treatment tumorsReceptor tyrosine kinase 2Post-treatment specimensPost-treatment samplesProspective cohortPositive tumorsTyrosine kinase 2Cancer-related genesPatientsTumor-normal pairsTherapeutic resistanceTumor tissueCNS changesHotspot mutations
2022
Inflammatory linear verrucous epidermal nevus (ILVEN) encompasses a spectrum of inflammatory mosaic disorders
Atzmony L, Ugwu N, Hamilton C, Paller A, Zech L, Antaya R, Choate K. Inflammatory linear verrucous epidermal nevus (ILVEN) encompasses a spectrum of inflammatory mosaic disorders. Pediatric Dermatology 2022, 39: 903-907. PMID: 35853659, PMCID: PMC9712156, DOI: 10.1111/pde.15094.Peer-Reviewed Original ResearchConceptsInflammatory linear verrucous epidermal nevusVerrucous epidermal nevusEpidermal nevusCARD14 mutationsHotspot mutationsLinear verrucous epidermal nevusPathogenesis-directed therapyCohort of patientsErythematous scaly plaquesRare skin diseaseLines of BlaschkoSomatic pathogenic variantsNSDHL mutationsHistopathological evaluationInflammatory disordersScaly plaquesHistopathologic evaluationHistopathological criteriaLinear porokeratosisSkin lesionsAffected skinPatientsSkin diseasesClinical descriptorsHeterogenous groupIntegrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis
Farshidfar F, Rhrissorrakrai K, Levovitz C, Peng C, Knight J, Bacchiocchi A, Su J, Yin M, Sznol M, Ariyan S, Clune J, Olino K, Parida L, Nikolaus J, Zhang M, Zhao S, Wang Y, Huang G, Wan M, Li X, Cao J, Yan Q, Chen X, Newman AM, Halaban R. Integrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis. Nature Communications 2022, 13: 898. PMID: 35197475, PMCID: PMC8866401, DOI: 10.1038/s41467-022-28566-4.Peer-Reviewed Original ResearchConceptsAcral melanomaMelanoma subtypesClinical profilingCommon melanoma subtypeImmune checkpoint blockadeCheckpoint blockadeInferior survivalMelanoma cell linesKey molecular driversPoor prognosisTherapeutic targetAnchorage-independent growthImmunomodulatory genesNon-white individualsHotspot mutationsMolecular driversCandidate oncogeneMelanomaApoptotic cell deathLZTR1Focal amplificationTumor promoterCell linesMetastasisTumor suppressor
2020
Corrigendum to “Phase II evaluation of copanlisib, a selective inhibitor of Pi3kca, in patients with persistent or recurrent endometrial carcinoma harboring PIK3CA hotspot mutations: An NRG oncology study (NRG-GY008)” [Gynecol. Oncol. Rep. 31 (2020) 100532]
Santin AD, Filiaci V, Bellone S, O'Cearbhaill R, Ratner ES, Mathews CA, Cantuaria G, Gunderson CC, Rutledge T, Buttin BM, Lankes HA, Birrer MJ. Corrigendum to “Phase II evaluation of copanlisib, a selective inhibitor of Pi3kca, in patients with persistent or recurrent endometrial carcinoma harboring PIK3CA hotspot mutations: An NRG oncology study (NRG-GY008)” [Gynecol. Oncol. Rep. 31 (2020) 100532]. Gynecologic Oncology Reports 2020, 33: 100590. PMID: 32885014, PMCID: PMC7452617, DOI: 10.1016/j.gore.2020.100590.Peer-Reviewed Original ResearchMutations in KRT10 in epidermolytic acanthoma
Cheraghlou S, Atzmony L, Roy SF, McNiff JM, Choate KA. Mutations in KRT10 in epidermolytic acanthoma. Journal Of Cutaneous Pathology 2020, 47: 524-529. PMID: 32045015, PMCID: PMC7914398, DOI: 10.1111/cup.13664.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingEpidermolytic acanthomaEpidermolytic hyperkeratosisHotspot mutationsCharacteristic histopathological patternEpidermolytic ichthyosisHistopathological patternsHistopathological analysisDiscovery cohortLesional tissueAdditional casesPolymerase chain reaction amplificationEpidermal degenerationChain reaction amplificationFragment length polymorphism analysisRestriction fragment length polymorphism analysisLength polymorphism analysisDermatosesIchthyosis bullosaAcanthomaKRT10Departmental archivesReaction amplificationIchthyosisPolymorphism analysisHistologic Classification and Molecular Signature of Polymorphous Adenocarcinoma (PAC) and Cribriform Adenocarcinoma of Salivary Gland (CASG)
Xu B, Barbieri AL, Bishop JA, Chiosea SI, Dogan S, Di Palma S, Faquin WC, Ghossein R, Hyrcza M, Jo VY, Lewis JS, Lozada JR, Michal M, Pareja FG, Perez-Ordonez B, Prasad ML, Purgina B, Reis-Filho JS, Scognamiglio T, Sebastiao APM, Seethala RR, Skálová A, Smith SM, Tekkeşin MS, Thompson LDR, Wasseman JK, Wenig BM, Weinreb I, Katabi N. Histologic Classification and Molecular Signature of Polymorphous Adenocarcinoma (PAC) and Cribriform Adenocarcinoma of Salivary Gland (CASG). The American Journal Of Surgical Pathology 2020, 44: 545-552. PMID: 31917707, PMCID: PMC7437128, DOI: 10.1097/pas.0000000000001431.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaBiomarkers, TumorBiopsyCanadaDNA Mutational AnalysisEuropeGene FusionGenetic Predisposition to DiseaseHumansIn Situ Hybridization, FluorescenceMutationObserver VariationPredictive Value of TestsReal-Time Polymerase Chain ReactionReproducibility of ResultsSalivary Gland NeoplasmsUnited StatesConceptsPapillary architectureIndeterminate featuresPolymorphous adenocarcinomaConsensus diagnosisCribriform adenocarcinomaInterobserver agreementSalivary glandsFair interobserver agreementNeck pathologistHistologic diversityHistologic classificationMorphologic spectrumDiagnostic concordanceSolid patternMolecular alterationsAdenocarcinomaGlomeruloid structuresTumorsLevel of agreementHotspot mutationsClear nucleiModerate agreementExpert pathologistsSuch molecular eventsMolecular signatures
2019
Plasma cell-free circulating tumor DNA (ctDNA) detection in longitudinally followed glioblastoma patients using TERT promoter mutation-specific droplet digital PCR assays.
Cordova C, Syeda M, Corless B, Wiggins J, Patel A, Kurz S, Delara M, Sawaged Z, Utate M, Placantonakis D, Golfinos J, Schafrick J, Silverman J, Jain R, Snuderl M, Zagzag D, Shao Y, Karlin-Neumann G, Polsky D, Chi A. Plasma cell-free circulating tumor DNA (ctDNA) detection in longitudinally followed glioblastoma patients using TERT promoter mutation-specific droplet digital PCR assays. Journal Of Clinical Oncology 2019, 37: 2026-2026. DOI: 10.1200/jco.2019.37.15_suppl.2026.Peer-Reviewed Original ResearchCell-free circulating tumor DNADroplet digital PCR assayDroplet digital PCRCtDNA levelsTERT mutationsPharmacodynamic biomarkersPlasma cell-free circulating tumor DNATERT promoter hotspot mutationsTERT promoter mutationsPromoter hotspot mutationsFFPE tumor samplesUnresected glioblastomaC228TPreoperative MRIIDH-wildtypeTumor DNADigital PCR assayIDHwt glioblastomasClinical stabilityTumor mutationsClinical outcomesClinical associationsGlioblastoma patientsHotspot mutationsTumor samples
2018
Frequent GNAQ and GNA14 Mutations in Hepatic Small Vessel Neoplasm
Joseph NM, Brunt EM, Marginean C, Nalbantoglu I, Snover DC, Thung SN, Yeh MM, Umetsu SE, Ferrell LD, Gill RM. Frequent GNAQ and GNA14 Mutations in Hepatic Small Vessel Neoplasm. The American Journal Of Surgical Pathology 2018, 42: 1201-1207. PMID: 29975248, DOI: 10.1097/pas.0000000000001110.Peer-Reviewed Original ResearchConceptsHepatic small vessel neoplasmVariant lesionsGNA14 mutationsVascular neoplasmLow-grade vascular neoplasmLow-grade neoplasmsVascular lesionsCavernous hemangiomaInfiltrative natureCytologic atypiaMolecular pathogenesisNeoplasmsPanel sequencingCopy number alterationsHotspot mutationsExome sequencingLesionsPathogenic mutationsSmall vesselsGNAQSame missense mutationNumber alterationsLiverMissense mutationsMutations
2017
Phase I Dose-Escalation Study of Taselisib, an Oral PI3K Inhibitor, in Patients with Advanced Solid Tumors
Juric D, Krop I, Ramanathan RK, Wilson TR, Ware JA, Bohorquez S, Savage HM, Sampath D, Salphati L, Lin RS, Jin H, Parmar H, Hsu JY, Von Hoff DD, Baselga J. Phase I Dose-Escalation Study of Taselisib, an Oral PI3K Inhibitor, in Patients with Advanced Solid Tumors. Cancer Discovery 2017, 7: 704-715. PMID: 28331003, PMCID: PMC5501742, DOI: 10.1158/2159-8290.cd-16-1080.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityAdverse eventsMutant tumorsHigh-grade adverse eventsTreatment-related adverse eventsConfirmed response rateMetastatic solid tumorsTumor xenograft modelPatient tumor samplesMeasurable diseasePharmacodynamic findingsPreclinical dataTumor patientsTumor growth inhibitorLow doseXenograft modelDose levelsResponse rateSolid tumorsPathway inhibitionPatientsPathway suppressionTumor samplesTumorsHotspot mutations
2016
Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant
Spoerke JM, Gendreau S, Walter K, Qiu J, Wilson TR, Savage H, Aimi J, Derynck MK, Chen M, Chan IT, Amler LC, Hampton GM, Johnston S, Krop I, Schmid P, Lackner MR. Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant. Nature Communications 2016, 7: 11579. PMID: 27174596, PMCID: PMC4869259, DOI: 10.1038/ncomms11579.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBreastBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDisease-Free SurvivalDNA Mutational AnalysisDNA, NeoplasmDrug Resistance, NeoplasmEstradiolEstrogen Receptor alphaEstrogen Receptor AntagonistsEstrogensFemaleFulvestrantHumansIndazolesMiddle AgedMutationProtein Kinase InhibitorsSulfonamidesConceptsMetastatic breast cancer patientsESR1 mutationsBreast cancer patientsCancer patientsPan-PI3K inhibitorPIK3CA-mutated tumorsProgression-free survivalMetastatic breast cancerWild-type patientsClinical trial samplesMutation allele frequencyInhibitor therapyFulvestrant treatmentBreast cancerClinical significanceClinical resistancePatientsBaseline samplesHotspot mutationsK inhibitorsTherapyLongitudinal analysisTrial samplesESR1Distinct clones
2012
Ultrasensitive Measurement of Hotspot Mutations in Tumor DNA in Blood Using Error-Suppressed Multiplexed Deep Sequencing
Narayan A, Carriero NJ, Gettinger SN, Kluytenaar J, Kozak KR, Yock TI, Muscato NE, Ugarelli P, Decker RH, Patel AA. Ultrasensitive Measurement of Hotspot Mutations in Tumor DNA in Blood Using Error-Suppressed Multiplexed Deep Sequencing. Cancer Research 2012, 72: 3492-3498. PMID: 22581825, PMCID: PMC3426449, DOI: 10.1158/0008-5472.can-11-4037.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerTumor DNATumor DNA levelsCell lung cancerCell-free tumor DNATreatment-associated changesDNA levelsTumor-specific mutationsPractical diagnostic testLung cancerPractical clinical implementationPatient samplesDiagnostic testsHotspot mutationsClinical implementationNext-generation sequencingBloodCancer biomarkersSuccessful useNormal DNAMutationsPatientsDeep sequencing
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