2025
Electronic health record-based registry for identification of individuals at risk for hereditary cancer syndromes
Singh V, Rafter T, Sharbatji M, Liu J, Brown Q, Brierley K, Healy C, Xicola R, Kashyap N, Llor X. Electronic health record-based registry for identification of individuals at risk for hereditary cancer syndromes. Journal Of Medical Genetics 2025, 62: 457-463. PMID: 40350248, DOI: 10.1136/jmg-2025-110718.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedElectronic Health RecordsFemaleGenetic Predisposition to DiseaseGenetic TestingHumansMaleMiddle AgedNeoplastic Syndromes, HereditaryRegistriesYoung AdultConceptsHereditary cancer syndromesElectronic health recordsGenetic testingElectronic health record-based registryCancer syndromesIdentification of individualsFamily history of cancerFamily historyFamily history criteriaAt-riskHistory of cancerAt-risk individualsHealth recordsPathogenic variantsProspective identification of individualsRegistryActive patientsSyndrome identificationFamily relationshipsIncreased diagnostic rateCancer-related survivalStreamlined processProspective identificationIndividualsTesting needsDevelopment of Syngeneic Murine Glioma Models with Somatic Mismatch Repair Deficiency to Study Therapeutic Responses to Alkylating Agents and Immunotherapy
Bhatt D, Sundaram R, López K, Lee T, Gueble S, Vasquez J. Development of Syngeneic Murine Glioma Models with Somatic Mismatch Repair Deficiency to Study Therapeutic Responses to Alkylating Agents and Immunotherapy. Current Protocols 2025, 5: e70097. PMID: 39995104, PMCID: PMC12183790, DOI: 10.1002/cpz1.70097.Peer-Reviewed Original ResearchConceptsImproved response to immune checkpoint blockadeGlioma modelResponse to immune checkpoint blockadeAlkylating agentsImmune checkpoint blockadeIncrease tumor immunogenicityMurine glioma modelMurine glioma cell lineResponse to alkylating agentsResistance to temozolomideDNA repair genotypesMMR deficiencyAntitumor immunityCheckpoint blockadeTumor immunogenicityMedian survivalImmunocompetent modelDismal prognosisMismatch repairMismatch repair deficiencyGlioma cell linesIntracranial tumorsAlkylating chemotherapySomatic lossSomatic acquisition
2024
Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric, Version 3.2024, NCCN Clinical Practice Guidelines In Oncology.
Hodan R, Gupta S, Weiss J, Axell L, Burke C, Chen L, Chung D, Clayback K, Felder S, Foda Z, Giardiello F, Grady W, Gustafson S, Hagemann A, Hall M, Hampel H, Idos G, Joseph N, Kassem N, Katona B, Kelly K, Kieber-Emmons A, Kupfer S, Lang K, Llor X, Markowitz A, Prats M, Niell-Swiller M, Outlaw D, Pirzadeh-Miller S, Samadder N, Shibata D, Stanich P, Swanson B, Szymaniak B, Welborn J, Wiesner G, Yurgelun M, Dwyer M, Darlow S, Diwan Z. Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric, Version 3.2024, NCCN Clinical Practice Guidelines In Oncology. Journal Of The National Comprehensive Cancer Network 2024, 22: 695-711. PMID: 39689429, DOI: 10.6004/jnccn.2024.0061.Peer-Reviewed Original ResearchMeSH KeywordsColorectal NeoplasmsEndometrial NeoplasmsFemaleGenetic Predisposition to DiseaseGenetic TestingHumansMaleMedical OncologyNeoplastic Syndromes, HereditaryRisk AssessmentStomach NeoplasmsConceptsMultigene panel testingPathogenic/likely pathogenic variantsGenetic/Familial High-Risk AssessmentColon cancer screeningColon cancer riskHigh risk of cancerNCCN Clinical Practice GuidelinesClinical practice guidelinesRisk of cancerPanel testingHigh riskPathogenic variantsPeutz-Jeghers syndromeLynch syndromeCancer screeningDe-implementationCancer riskEndometrial cancerPTEN hamartoma tumor syndromeHigh-risk assessmentPractice guidelinesHamartoma tumor syndromePeutz-JeghersNCCN guidelinesCHEK2Epigenetic MLH1 silencing concurs with mismatch repair deficiency in sporadic, naturally occurring colorectal cancer in rhesus macaques
Deycmar S, Johnson B, Ray K, Schaaf G, Ryan D, Cullin C, Dozier B, Ferguson B, Bimber B, Olson J, Caudell D, Whitlow C, Solingapuram Sai K, Romero E, Villinger F, Burgos A, Ainsworth H, Miller L, Hawkins G, Chou J, Gomes B, Hettich M, Ceppi M, Charo J, Cline J. Epigenetic MLH1 silencing concurs with mismatch repair deficiency in sporadic, naturally occurring colorectal cancer in rhesus macaques. Journal Of Translational Medicine 2024, 22: 292. PMID: 38504345, PMCID: PMC10953092, DOI: 10.1186/s12967-024-04869-6.Peer-Reviewed Original ResearchConceptsHuman colorectal cancerColorectal cancerCpG island methylator phenotypeRhesus macaquesDNA topologyEpigenetic silencingHuman CRC patientsDNA methylationMethylation-specific qPCRCancer immunotherapyPathology reviewMismatch repair deficiencyIsland methylator phenotypeCancer histologyCRC patientsCACNA1GCo-morbiditiesGermline levelPromoter hypermethylationMolecular pathogenesisConclusionsThese dataChromosomal instabilityClinical assessmentEpigenetic silencing of MLH1Repair deficiency
2023
Liver Transplantation for Mahvash Disease, an Inborn Error of Metabolism
Mistry P, Garcia-Tsao G. Liver Transplantation for Mahvash Disease, an Inborn Error of Metabolism. New England Journal Of Medicine 2023, 389: 2010-2013. PMID: 37991861, DOI: 10.1056/nejme2310332.Peer-Reviewed Original ResearchBiomarkers of immune checkpoint inhibitor response and toxicity: Challenges and opportunities
Goodman R, Jung S, Balko J, Johnson D. Biomarkers of immune checkpoint inhibitor response and toxicity: Challenges and opportunities. Immunological Reviews 2023, 318: 157-166. PMID: 37470280, PMCID: PMC10528475, DOI: 10.1111/imr.13249.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersBiomarkers, TumorBrain NeoplasmsColorectal NeoplasmsHumansImmune Checkpoint InhibitorsImmunotherapyNeoplastic Syndromes, HereditaryConceptsImmune checkpoint inhibitorsCheckpoint inhibitorsImmune checkpoint inhibitor responsePD-L1 stainingCheckpoint inhibitor responseBiomarkers of responseClinical trial enrollmentPD-L1Therapy discontinuationSevere toxicityTherapy selectionSevere morbidityInhibitor responseCancer therapyTrial enrollmentLack of responseTherapyTherapeutic biomarkersBiomarkersDrug developmentToxicityInhibitorsTumorMorbidityOptimal useFKBP14 kyphoscoliotic Ehlers–Danlos syndrome misdiagnosed as Larsen syndrome: a case report
Wiegand A, Kastury R, Neogi A, Mani A, Bale A, Cox A. FKBP14 kyphoscoliotic Ehlers–Danlos syndrome misdiagnosed as Larsen syndrome: a case report. Molecular Case Studies 2023, 9: a006281. PMID: 37433679, PMCID: PMC10393184, DOI: 10.1101/mcs.a006281.Peer-Reviewed Original ResearchMeSH KeywordsAdultDiagnostic ErrorsEhlers-Danlos SyndromeFemaleGenotypeHumansNeoplastic Syndromes, HereditaryOsteochondrodysplasiasPeptidylprolyl IsomeraseConceptsHereditary connective tissue disordersConnective tissue disordersKyphoscoliotic Ehlers-Danlos syndromeTissue disordersEhlers-Danlos syndromeLarsen syndromeClinical diagnosisGenetic testingHereditary cancer predisposition syndromesSignificant vascular eventsPremenopausal breast cancerPast medical historyHomozygous pathogenic variantCancer predisposition syndromeWhole-exome sequencingMolecular genetic testingCardiovascular eventsCarotid dissectionVascular eventsCardiovascular manifestationsCase reportMedical historyRecent diagnosisBreast cancerEarly diagnosis
2022
Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti-PD-1 Immunotherapy in Endometrial Carcinoma.
Chow RD, Michaels T, Bellone S, Hartwich T, Bonazzoli E, Iwasaki A, Song E, Santin AD. Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti-PD-1 Immunotherapy in Endometrial Carcinoma. Cancer Discovery 2022, 13: 312-331. PMID: 36301137, PMCID: PMC9905265, DOI: 10.1158/2159-8290.cd-22-0686.Peer-Reviewed Original ResearchMeSH KeywordsBrain NeoplasmsDNA Mismatch RepairEndometrial NeoplasmsFemaleHumansImmunotherapyNeoplastic Syndromes, HereditaryConceptsAnti-PD-1 immunotherapyImmune checkpoint blockadeMMRd tumorsNK cellsEndometrial carcinomaICB responseMutation burdenT-cell-driven immunityPhase II clinical trialMMRd endometrial cancersPD-1 inhibitorsMismatch repair-deficient cancersTumor-extrinsic factorsHigh response rateEffector CD8Antitumor immunityEndometrial cancerCancer immunotherapyImmune cellsLonger survivalClinical trialsPrimary resistanceT cellsResponse rateMMRdMutational signature profiling classifies subtypes of clinically different mismatch-repair-deficient tumours with a differential immunogenic response potential
Giner-Calabuig M, De Leon S, Wang J, Fehlmann TD, Ukaegbu C, Gibson J, Alustiza-Fernandez M, Pico MD, Alenda C, Herraiz M, Carrillo-Palau M, Salces I, Reyes J, Ortega SP, Obrador-Hevia A, Cecchini M, Syngal S, Stoffel E, Ellis NA, Sweasy J, Jover R, Llor X, Xicola RM. Mutational signature profiling classifies subtypes of clinically different mismatch-repair-deficient tumours with a differential immunogenic response potential. British Journal Of Cancer 2022, 126: 1595-1603. PMID: 35197584, PMCID: PMC9130322, DOI: 10.1038/s41416-022-01754-1.Peer-Reviewed Original ResearchConceptsLynch-like syndromeMMR-deficient tumorsLynch syndromeMicrosatellite instabilityPercent of tumorsMSH2/MSH6 expressionColorectal cancer tumorsPMS2 protein expressionMutational signaturesResultsFifty-three percentClinical managementNeoantigen presentationMSH6 expressionHallmark of tumorsTumor behaviorMMR deficiencyClinical phenotypeDeficient tumorsTumorsSporadic tumorsCancer tumorsMutational profileProtein expressionRepair deficiencySyndrome
2021
Clinicopathological significance of neutrophil-rich colorectal carcinoma
Rottmann BG, Patel N, Ahmed M, Deng Y, Ciarleglio M, Vyas M, Jain D, Zhang X. Clinicopathological significance of neutrophil-rich colorectal carcinoma. Journal Of Clinical Pathology 2021, 76: 34-39. PMID: 34312298, PMCID: PMC10910606, DOI: 10.1136/jclinpath-2021-207702.Peer-Reviewed Original ResearchMeSH KeywordsColorectal NeoplasmsDNA Mismatch RepairHumansNeoplastic Syndromes, HereditaryNeutrophilsPrognosisConceptsRecurrence-free survivalColorectal carcinomaHistological gradeTumor locationRight-sided tumor locationTumor cellsDNA mismatch repair (MMR) statusIndependent risk factorKaplan-Meier analysisHigh histological gradeAdvanced TNM stageMismatch repair statusPrognostic significanceCRC casesClinicopathological significanceTNM stageMetastasis stagePatient prognosisRisk factorsClinicopathological parametersMultivariate analysisRepair statusPatientsCarcinomaHigh ratePhenotypic Differences in Juvenile Polyposis Syndrome With or Without a Disease-causing SMAD4/BMPR1A Variant
MacFarland SP, Ebrahimzadeh JE, Zelley K, Begum L, Bass LM, Brand RE, Dudley B, Fishman DS, Ganzak A, Karloski E, Latham A, Llor X, Plon S, Riordan MK, Scollon SR, Stadler ZK, Syngal S, Ukaegbu C, Weiss JM, Yurgelun MB, Brodeur GM, Mamula P, Katona BW. Phenotypic Differences in Juvenile Polyposis Syndrome With or Without a Disease-causing SMAD4/BMPR1A Variant. Cancer Prevention Research 2021, 14: 215-222. PMID: 33097490, PMCID: PMC8557953, DOI: 10.1158/1940-6207.capr-20-0348.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge FactorsAgedBone Morphogenetic Protein Receptors, Type IChildChild, PreschoolColectomyColonoscopyFemaleFollow-Up StudiesGerm-Line MutationHumansIntestinal PolyposisMaleMedical History TakingMiddle AgedNeoplastic Syndromes, HereditaryPractice Guidelines as TopicPrecision MedicineSmad4 ProteinWatchful WaitingYoung AdultConceptsJuvenile polyposis syndromePolyposis syndromeFamily historyDisease-causing variantsCancer riskGermline disease-causing variantsGastrointestinal cancer predisposition syndromesUpper gastrointestinal polypsHamartomatous polyposis syndromesCancer predisposition syndromeLifelong surveillanceAdult centersDuodenal polypsGastrointestinal cancerCancer historySubgroup analysisIndividualized managementLower riskGastrointestinal polypsPredisposition syndromeSyndromeYounger ageDistinct phenotypic differencesLower likelihoodGastrectomyComparison of Universal Genetic Testing vs Guideline-Directed Targeted Testing for Patients With Hereditary Cancer Syndrome
Samadder N, Riegert-Johnson D, Boardman L, Rhodes D, Wick M, Okuno S, Kunze K, Golafshar M, Uson P, Mountjoy L, Ertz-Archambault N, Patel N, Rodriguez E, Lizaola-Mayo B, Lehrer M, Thorpe C, Yu N, Esplin E, Nussbaum R, Sharp R, Azevedo C, Klint M, Hager M, Macklin-Mantia S, Bryce A, Bekaii-Saab T, Sekulic A, Stewart A. Comparison of Universal Genetic Testing vs Guideline-Directed Targeted Testing for Patients With Hereditary Cancer Syndrome. JAMA Oncology 2021, 7: 230-237. PMID: 33126242, PMCID: PMC7600058, DOI: 10.1001/jamaoncol.2020.6252.Peer-Reviewed Original ResearchMeSH KeywordsCohort StudiesGenetic Predisposition to DiseaseGenetic TestingGerm-Line MutationHumansMaleNeoplastic Syndromes, HereditaryProspective StudiesConceptsPrevalence of pathogenic germline variantsFamily variant testingPathogenic germline variantsSolid tumor cancersHigh-penetrance cancer susceptibility genesFamily history of cancerMayo Clinic Cancer CenterRisk-reducing interventionsUniversal genetic testingMultigene panel testingHigh-penetrance variantsHistory of cancerClinic Cancer CenterUniversal testing approachGermline variantsGuideline-directed approachYounger age of diagnosisTumor cancersCancer susceptibility genesClinically actionable findingsTargeted testingCancer screeningAge of diagnosisGermline testingVariant testing
2020
Clinical Implications of Germline Testing in Newly Diagnosed Prostate Cancer
Loeb S, Giri V. Clinical Implications of Germline Testing in Newly Diagnosed Prostate Cancer. European Urology Oncology 2020, 4: 1-9. PMID: 33390340, DOI: 10.1016/j.euo.2020.11.011.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsGenetic TestingGerm CellsGerm-Line MutationHumansMaleNeoplastic Syndromes, HereditaryProstatic NeoplasmsConceptsGermline testingLocalized diseaseMetastatic PCaFamily historyGermline evaluationMetastatic diseaseCurrent guidelinesProstate cancerCancer riskPractice settingsGenetic testingDNA mismatch repair deficiencyManagement of menProstate cancer managementFamily cancer riskEarly-stage PCaMismatch repair deficiencyHereditary cancer riskPathologic featuresHistologic featuresMedical oncologyCancer screeningPCa managementPCa riskConsensus panelGenomic alterations in Turcot syndrome: Insights from whole exome sequencing
Karschnia P, Erson-Omay EZ, Huttner AJ, Kaulen LD, Duran D, Fulbright RK, Günel M, Baehring JM. Genomic alterations in Turcot syndrome: Insights from whole exome sequencing. Journal Of The Neurological Sciences 2020, 417: 117056. PMID: 32739502, DOI: 10.1016/j.jns.2020.117056.Peer-Reviewed Original ResearchBrain NeoplasmsColorectal NeoplasmsExome SequencingGenomicsHumansMutationNeoplastic Syndromes, HereditaryMetastatic Colorectal Cancers with Mismatch Repair Deficiency Result in Worse Survival Regardless of Peritoneal Metastases
Sherman S, Schuitevoerder D, Chan C, Turaga K. Metastatic Colorectal Cancers with Mismatch Repair Deficiency Result in Worse Survival Regardless of Peritoneal Metastases. Annals Of Surgical Oncology 2020, 27: 5074-5083. PMID: 32583196, PMCID: PMC9782694, DOI: 10.1245/s10434-020-08733-x.Peer-Reviewed Original ResearchMeSH KeywordsBrain NeoplasmsColorectal NeoplasmsDNA Mismatch RepairHumansNeoplasm StagingNeoplastic Syndromes, HereditaryPeritoneal NeoplasmsConceptsNational Cancer DatabasePeritoneal metastasisAppendix cancerPM patientsPrimary tumorWorse survivalDistant nodal metastasisStage 4 diseaseMetastatic colorectal cancerMMR testingStage 4 patientsColon primary tumorsKaplan-Meier analysisStage 4 colorectal cancerFisher's exact testBackgroundMismatch-repair-deficiencyImmunotherapy useNodal metastasisMetastatic colorectalCancer DatabaseDMMR tumorsTested patientsExact testColorectal adenocarcinomaColorectal cancerEstimation 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 syndromesAlterationsNCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 1.2020.
Daly M, Pilarski R, Yurgelun M, Berry M, Buys S, Dickson P, Domchek S, Elkhanany A, Friedman S, Garber J, Goggins M, Hutton M, Khan S, Klein C, Kohlmann W, Kurian A, Laronga C, Litton J, Mak J, Menendez C, Merajver S, Norquist B, Offit K, Pal T, Pederson H, Reiser G, Shannon K, Visvanathan K, Weitzel J, Wick M, Wisinski K, Dwyer M, Darlow S. NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 1.2020. Journal Of The National Comprehensive Cancer Network 2020, 18: 380-391. PMID: 32259785, DOI: 10.6004/jnccn.2020.0017.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorFemaleGenetic Association StudiesGenetic CounselingGenetic Predisposition to DiseaseGenetic TestingHumansNeoplastic Syndromes, HereditaryOvarian NeoplasmsPancreatic NeoplasmsPenetranceConceptsGenetic/Familial High-Risk AssessmentHigh-risk assessmentGenetic testingNCCN Guidelines InsightsHereditary cancer syndromesHigh-penetrance genesNCCN panelNCCN guidelinesSystemic therapyAshkenazi Jewish ancestryMost recent recommendationsRelevant new dataPancreatic cancerOvarian cancerCancer syndromesRecent recommendationsCancerBreastSyndromeOvarianManagement recommendationsJewish ancestryRisk management recommendations
2019
Response to Letter to the Editor: High Oncotype DX Recurrence Score, Hereditary Cancer Syndromes, and Referral for Germline Genetic Testing
Casasanta N, Amdur R, Kaltman R. Response to Letter to the Editor: High Oncotype DX Recurrence Score, Hereditary Cancer Syndromes, and Referral for Germline Genetic Testing. Clinical Breast Cancer 2019, 20: e198-e199. PMID: 31964593, DOI: 10.1016/j.clbc.2019.12.007.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsGenetic TestingGerm CellsHumansNeoplasm Recurrence, LocalNeoplastic Syndromes, HereditaryReferral and ConsultationRelationship Between Hereditary Cancer Syndromes and Oncotype DX Recurrence Score
Casasanta N, Kipnis S, Linville L, Lipinski S, Knoedler A, Marino A, McHenry A, Biagi T, Stark E, Amdur R, Denduluri N, Rodriguez P, Isaacs C, Kaltman R. Relationship Between Hereditary Cancer Syndromes and Oncotype DX Recurrence Score. Clinical Breast Cancer 2019, 20: 125-130. PMID: 31526714, DOI: 10.1016/j.clbc.2019.07.004.Peer-Reviewed Original ResearchConceptsGermline mutation statusOncotype DX recurrence scoreBreast cancer patientsRecurrence scoreMutation statusOncotype DXAssociation of RSGermline mutationsCancer patientsHormone receptor-positive breast cancer patientsHereditary cancer riskGermline genetic testingGenetic risk assessmentHereditary cancer syndromesAssociated with germline mutationsBenefit of chemotherapyRetrospective analysis of dataMultivariate logistic regression modelLikelihood of recurrenceFisher's exact testMultivariate logistic regressionCounseling of family membersLogistic regression modelsNon-BRCA1/2BRCA2 genesPrevalence of Suspected Hereditary Cancer Syndromes and Germline Mutations Among a Diverse Cohort of Probands Reporting a Family History of Prostate Cancer: Toward Informing Cascade Testing for Men
Chandrasekar T, Gross L, Gomella L, Hegarty S, Leong J, Giri V. Prevalence of Suspected Hereditary Cancer Syndromes and Germline Mutations Among a Diverse Cohort of Probands Reporting a Family History of Prostate Cancer: Toward Informing Cascade Testing for Men. European Urology Oncology 2019, 3: 291-297. PMID: 31278035, DOI: 10.1016/j.euo.2019.06.010.Peer-Reviewed Original ResearchMeSH KeywordsFemaleGenetic TestingGerm-Line MutationHumansMaleNeoplastic Syndromes, HereditaryPedigreePrevalenceProspective StudiesProstatic NeoplasmsConceptsHereditary cancer syndromesProstate cancerCancer syndromesFamily historyGermline mutationsExact testHereditary breastGenetic testingAfrican AmericansPCa family historyAfrican American patientsOvarian cancer syndromeCascade genetic testingFisher's exact testHereditary prostate cancerBRCA mutationsLynch syndromeOvarian cancerSyndromeCancerCascade testingDiverse cohortAA participantsSpectrum of genesFHx
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