2022
Systems approach to enhance Lynch syndrome diagnosis through tumour testing
Singh V, Mezzacappa C, Gershkovich P, Di Giovanna J, Ganzak A, Gibson J, Sinard J, Xicola RM, Llor X. Systems approach to enhance Lynch syndrome diagnosis through tumour testing. Journal Of Medical Genetics 2022, 60: 533-539. PMID: 36115663, PMCID: PMC10020126, DOI: 10.1136/jmg-2022-108770.Peer-Reviewed Original ResearchConceptsOriginal cohortColorectal adenocarcinomaLynch syndromeTumor testingGenetic testingPercentage of patientsProportion of patientsLynch syndrome diagnosisCG evaluationCancer genetic testingRace/ethnicityCRC testingCohort studyMMR immunohistochemistryLS diagnosisNew diagnosisMMR lossAcademic centersPatientsSyndrome diagnosisCohortCase identificationMethylation testingReferral differencesReferral mechanismsMutational 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
Molecular drivers of tumor progression in microsatellite stable APC mutation-negative colorectal cancers
Grant A, Xicola RM, Nguyen V, Lim J, Thorne C, Salhia B, Llor X, Ellis N, Padi M. Molecular drivers of tumor progression in microsatellite stable APC mutation-negative colorectal cancers. Scientific Reports 2021, 11: 23507. PMID: 34873211, PMCID: PMC8648784, DOI: 10.1038/s41598-021-02806-x.Peer-Reviewed Original ResearchMeSH KeywordsAdenomatous Polyposis ColiAdenomatous Polyposis Coli ProteinColorectal NeoplasmsDisease ProgressionDNA Copy Number VariationsDNA MethylationGenes, APCHumansMicrosatellite InstabilityMicrosatellite RepeatsMutationNeoplastic ProcessesPhenotypePromoter Regions, GeneticWnt Signaling PathwayConceptsAdenomatous polyposis coliMitochondrial activationDNA methylation profilesTumor suppressor gene adenomatous polyposis coliRNA expressionExpression of Axin2Cancer Genome AtlasIntracellular WntMethylation profilesAberrant regulationGene fusionsGenetic inactivationExtracellular WntNumber variationsGenome AtlasPolyposis coliSomatic mutationsAPC mutationsMutationsMolecular driversMutations of BRAFWntRSPO3Tumor progressionExpression
2018
Lack of APC somatic mutation is associated with early-onset colorectal cancer in African Americans
Xicola RM, Manojlovic Z, Augustus GJ, Kupfer SS, Emmadi R, Alagiozian-Angelova V, Triche T, Salhia B, Carpten J, Llor X, Ellis NA. Lack of APC somatic mutation is associated with early-onset colorectal cancer in African Americans. Carcinogenesis 2018, 39: 1331-1341. PMID: 30239619, PMCID: PMC6292413, DOI: 10.1093/carcin/bgy122.Peer-Reviewed Original ResearchMeSH KeywordsAdenomatous Polyposis Coli ProteinBlack or African AmericanCadherinsColorectal NeoplasmsDNA Copy Number VariationsDNA MethylationDNA-Binding ProteinsExome SequencingFemaleGATA6 Transcription FactorHumansMaleMicrosatellite InstabilityMicrosatellite RepeatsMiddle AgedMixed Function OxygenasesProto-Oncogene ProteinsSOX9 Transcription FactorTranscription FactorsWnt Signaling Pathway
2014
Excess of Proximal Microsatellite-Stable Colorectal Cancer in African Americans from a Multiethnic Study
Xicola RM, Gagnon M, Clark JR, Carroll T, Gao W, Fernandez C, Mijic D, Rawson JB, Janoski A, Pusatcioglu CK, Rajaram P, Gluskin AB, Regan M, Chaudhry V, Abcarian H, Blumetti J, Cintron J, Melson J, Xie H, Guzman G, Emmadi R, Alagiozian-Angelova V, Kupfer SS, Braunschweig C, Ellis NA, Llor X. Excess of Proximal Microsatellite-Stable Colorectal Cancer in African Americans from a Multiethnic Study. Clinical Cancer Research 2014, 20: 4962-4970. PMID: 25013126, PMCID: PMC4167473, DOI: 10.1158/1078-0432.ccr-14-0353.Peer-Reviewed Original ResearchConceptsProximal colorectal cancerColorectal cancerMicrosatellite instabilityLymphocytic infiltrateKRAS mutationsAfrican AmericansMicrosatellite stable colorectal cancerDistal colorectal cancerFisher's exact testMicrosatellite stable tumorsMann-Whitney U testYoung African AmericansMedian ageAA patientsHigher BMICancer disparitiesChicago HospitalsStable tumorsAge 50High incidenceMultiethnic StudyExact testYounger ageCancerOlder age