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
Colorectal cancer molecular classification using BRAF, KRAS, microsatellite instability and CIMP status: Prognostic implications and response to chemotherapy
Murcia O, Juárez M, Rodríguez-Soler M, Hernández-Illán E, Giner-Calabuig M, Alustiza M, Egoavil C, Castillejo A, Alenda C, Barberá V, Mangas-Sanjuan C, Yuste A, Bujanda L, Clofent J, Andreu M, Castells A, Llor X, Zapater P, Jover R. Colorectal cancer molecular classification using BRAF, KRAS, microsatellite instability and CIMP status: Prognostic implications and response to chemotherapy. PLOS ONE 2018, 13: e0203051. PMID: 30188916, PMCID: PMC6126803, DOI: 10.1371/journal.pone.0203051.Peer-Reviewed Original ResearchConceptsDisease-free survivalColorectal cancerMicrosatellite instabilityCIMP statusTNM stageKRAS mutationsBRAF mutationsMSS tumorsMolecular classificationAdvanced stage IIRetrospective observational studyPopulation-based cohortCpG island methylator phenotype (CIMP) statusCancer molecular classificationSomatic KRASAdjuvant chemotherapyAdjuvant treatmentCRC patientsPrognostic implicationsWorse prognosisPrognostic valueClinical criteriaObservational studyMolecular subtypesMAIN OUTCOME
2015
Mutation Spectrum and Risk of Colorectal Cancer in African American Families with Lynch Syndrome
Santa Cruz Guindalini R, Win AK, Gulden C, Lindor NM, Newcomb PA, Haile RW, Raymond V, Stoffel E, Hall M, Llor X, Ukaegbu CI, Solomon I, Weitzel J, Kalady M, Blanco A, Terdiman J, Shuttlesworth GA, Lynch PM, Hampel H, Lynch HT, Jenkins MA, Olopade OI, Kupfer SS. Mutation Spectrum and Risk of Colorectal Cancer in African American Families with Lynch Syndrome. Gastroenterology 2015, 149: 1446-1453. PMID: 26248088, PMCID: PMC4648287, DOI: 10.1053/j.gastro.2015.07.052.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdenosine TriphosphatasesAdultAge FactorsAgedAged, 80 and overBlack or African AmericanColorectal NeoplasmsColorectal Neoplasms, Hereditary NonpolyposisDNA Mismatch RepairDNA Repair EnzymesDNA-Binding ProteinsFamilyFemaleHumansIncidenceMaleMiddle AgedMismatch Repair Endonuclease PMS2MutationMutL Protein Homolog 1MutS Homolog 2 ProteinNuclear ProteinsRetrospective StudiesRisk FactorsSex FactorsConceptsColorectal cancerLynch syndromeCumulative riskRisk of CRCUS referral centersMMR gene mutationsMutation spectrumNongenetic risk factorsYears of ageMismatch repair genesMMR gene productsMutation-carrying familiesReferral centerRetrospective studyCRC riskRisk factorsFamily historyCancer riskHigh incidenceCRC conditionsSyndromeAbstractTextMMR genesAscertainment criteriaCancerPrevalence of MLH1 constitutional epimutations as a cause of Lynch syndrome in unselected versus selected consecutive series of patients with colorectal cancer
Castillejo A, Hernández-Illán E, Rodriguez-Soler M, Pérez-Carbonell L, Egoavil C, Barberá VM, Castillejo MI, Guarinos C, Martínez-de-Dueñas E, Juan MJ, Sánchez-Heras AB, García-Casado Z, Ruiz-Ponte C, Brea-Fernández A, Juárez M, Bujanda L, Clofent J, Llor X, Andreu M, Castells A, Carracedo A, Alenda C, Payá A, Jover R, Soto JL. Prevalence of MLH1 constitutional epimutations as a cause of Lynch syndrome in unselected versus selected consecutive series of patients with colorectal cancer. Journal Of Medical Genetics 2015, 52: 498. PMID: 25908759, DOI: 10.1136/jmedgenet-2015-103076.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingBase SequenceColorectal Neoplasms, Hereditary NonpolyposisDNA MethylationDNA Mismatch RepairEpigenesis, GeneticGenetic TestingHumansMicrosatellite RepeatsMolecular Sequence DataMutationMutL Protein Homolog 1Nuclear ProteinsPrevalencePromoter Regions, GeneticSequence Analysis, DNAStatistics, NonparametricConceptsColorectal cancerMLH1 expressionConstitutional epimutationsMultiplex ligation-dependent probe amplificationLigation-dependent probe amplificationMethylation-specific multiplex ligation-dependent probe amplificationDiagnosis of CRCConstitutional MLH1 methylationSeries of patientsMismatch repair genesProbe amplificationBethesda guidelinesConsecutive seriesUnselected seriesLynch syndromeUnselected casesUnselected groupGeneral populationUnselected populationPatientsMLH1 methylationNegligible prevalenceGermline alterationsPrevalenceMLH1 epimutations
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 ageIGFBP3 Methylation Is a Novel Diagnostic and Predictive Biomarker in Colorectal Cancer
Perez-Carbonell L, Balaguer F, Toiyama Y, Egoavil C, Rojas E, Guarinos C, Andreu M, Llor X, Castells A, Jover R, Boland CR, Goel A. IGFBP3 Methylation Is a Novel Diagnostic and Predictive Biomarker in Colorectal Cancer. PLOS ONE 2014, 9: e104285. PMID: 25127039, PMCID: PMC4134211, DOI: 10.1371/journal.pone.0104285.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorColorectal NeoplasmsCpG IslandsDNA MethylationFemaleHumansInsulin-Like Growth Factor Binding Protein 3Intestinal MucosaMaleMicrosatellite InstabilityMicrosatellite RepeatsMiddle AgedMutationNeoplasm StagingPrognosisPromoter Regions, GeneticProto-Oncogene Proteins B-rafTreatment OutcomeConceptsCRC patientsColorectal cancerPredictive biomarkersStage IICRC cohortPoor disease-free survivalDisease-free survivalIndependent risk factorPopulation-based cohortPotential clinical significancePromising diagnostic biomarkerFree survivalRisk factorsColonic tumorsCRC-specific genesClinical significanceNormal mucosaCancer-related genesPatientsDiagnostic biomarkersTumor tissueBiomarkersCohortCancerHuman cancers
2012
Defectos de la metilación del ADN en el cáncer colorrectal esporádico y hereditario
Xicola RM, Llor X. Defectos de la metilación del ADN en el cáncer colorrectal esporádico y hereditario. Gastroenterología Y Hepatología 2012, 35: 480-487. PMID: 22459641, DOI: 10.1016/j.gastrohep.2012.01.010.BooksMeSH KeywordsAdenocarcinomaAdenomaAnticarcinogenic AgentsAntineoplastic AgentsBiomarkersCell Transformation, NeoplasticClonal EvolutionColorectal NeoplasmsCpG IslandsDietDNA MethylationDNA, NeoplasmDrug DesignFolic AcidGenes, NeoplasmGenes, Tumor SuppressorGenome-Wide Association StudyHumansIncidenceMolecular Targeted TherapyMutationNeoplastic Syndromes, HereditaryPolyphenolsSeleniumConceptsMethylation defectsFundamental epigenetic mechanismCrucial cell functionsExpression of genesEpigenetic mechanismsDNA methylationGene analysisMethylationMethylation processCancer developmentCell functionDevelopment of chemotherapyEffect of dietGenesColorectal carcinogenesisAntineoplastic activity
2011
Evidence for classification of c.1852_1853AA>GC in MLH1 as a neutral variant for Lynch syndrome
Castillejo A, Guarinos C, Martinez-Canto A, Barbera VM, Egoavil C, Castillejo MI, Perez-Carbonell L, Sanchez-Heras AB, Segura A, Ochoa E, Lazaro R, Ruiz-Ponte C, Bujanda L, Andreu M, Castells A, Carracedo A, Llor X, Clofent J, Alenda C, Paya A, Jover R, Soto JL. Evidence for classification of c.1852_1853AA>GC in MLH1 as a neutral variant for Lynch syndrome. BMC Medical Genomics 2011, 12: 12. PMID: 21247423, PMCID: PMC3034663, DOI: 10.1186/1471-2350-12-12.Peer-Reviewed Original ResearchConceptsMicrosatellite instabilityLS familiesAmsterdam II criteriaPathogenic mutationsCase-case studyEarly-onset cancersCase-control comparisonBackgroundLynch syndromeCRC probandsHereditary CRCTumor DNA samplesCRC patientsSporadic CRCLS patientsClinical managementLynch syndromeClinical significanceOnset cancerCancer syndromesPositive casesMononucleotide markersControl populationPathogenic variantsSignificant associationMSH6 gene
2010
Aberrant DNA Methylation in Hereditary Nonpolyposis Colorectal Cancer Without Mismatch Repair Deficiency
Goel A, Xicola RM, Nguyen T, Doyle BJ, Sohn VR, Bandipalliam P, Rozek LS, Reyes J, Cordero C, Balaguer F, Castells A, Jover R, Andreu M, Syngal S, Boland CR, Llor X. Aberrant DNA Methylation in Hereditary Nonpolyposis Colorectal Cancer Without Mismatch Repair Deficiency. Gastroenterology 2010, 138: 1854-1862.e1. PMID: 20102720, PMCID: PMC2859993, DOI: 10.1053/j.gastro.2010.01.035.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultAgedAged, 80 and overBase SequenceBasic Helix-Loop-Helix Transcription FactorsColorectal Neoplasms, Hereditary NonpolyposisCore Binding Factor Alpha 3 SubunitDNA MethylationDNA Mismatch RepairEpigenesis, GeneticFemaleGene Expression Regulation, NeoplasticGenetic Predisposition to DiseaseGenomic InstabilityHumansLong Interspersed Nucleotide ElementsMaleMicrosatellite RepeatsMiddle AgedMolecular Sequence DataMutationMutL Protein Homolog 1Nerve Tissue ProteinsNuclear ProteinsPedigreePhenotypeProto-Oncogene ProteinsProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)Ras ProteinsSpainSuppressor of Cytokine Signaling 1 ProteinSuppressor of Cytokine Signaling ProteinsUnited StatesConceptsHereditary nonpolyposis colorectal cancerNonpolyposis colorectal cancerHNPCC tumorsMismatch repair deficiencyColorectal cancerMicrosatellite instabilityGermline mismatch repair (MMR) gene mutationsLynch syndrome cancersMismatch repair gene mutationsRepair deficiencyBest diagnostic approachBRAF mutation statusRepair gene mutationsSporadic microsatellite instabilityV600E BRAF mutationLINE-1 methylationSyndrome cancersAmsterdam criteriaLynch syndromeKRAS mutationsTreatment responseBRAF mutationsHigh indexTumor behaviorCarcinogenic pathways
2006
Detection of BRAF V600E Mutation in Colorectal Cancer Comparison of Automatic Sequencing and Real-Time Chemistry Methodology
Benlloch S, Payá A, Alenda C, Bessa X, Andreu M, Jover R, Castells A, Llor X, Aranda FI, Massutí B. Detection of BRAF V600E Mutation in Colorectal Cancer Comparison of Automatic Sequencing and Real-Time Chemistry Methodology. Journal Of Molecular Diagnostics 2006, 8: 540-543. PMID: 17065421, PMCID: PMC1876165, DOI: 10.2353/jmoldx.2006.060070.Peer-Reviewed Original ResearchClinical Performance of Original and Revised Bethesda Guidelines for the Identification of MSH2/MLH1 Gene Carriers in Patients with Newly Diagnosed Colorectal Cancer: Proposal of a New and Simpler Set of Recommendations
Rodríguez-Moranta F, Castells A, Andreu M, Piñol V, Castellví-Bel S, Alenda C, Llor X, Xicola RM, Jover R, Payá A, Bessa X, Balaguer F, Cubiella J, Argüello L, Morillas JD, Bujanda L. Clinical Performance of Original and Revised Bethesda Guidelines for the Identification of MSH2/MLH1 Gene Carriers in Patients with Newly Diagnosed Colorectal Cancer: Proposal of a New and Simpler Set of Recommendations. The American Journal Of Gastroenterology 2006, 101: ajg2006204. PMID: 16696788, DOI: 10.1111/j.1572-0241.2006.00522.x.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAgedCarrier ProteinsColorectal NeoplasmsEpidemiologic StudiesHeterozygoteHumansMiddle AgedMutationMutL Protein Homolog 1MutS Homolog 2 ProteinNuclear ProteinsPractice Guidelines as TopicPredictive Value of TestsProspective StudiesSensitivity and SpecificitySpainConceptsBethesda guidelinesColorectal cancerNegative predictive valuePredictive valueClinical performanceMLH1 germline mutationsGene mutation carriersLogistic regression analysisNational Cancer InstitutePositive predictive valueCancer genetic testingMutation carriersIdentification of individualsEpidemiology SurveysCancer InstitutePatientsGenetic testingGermline mutationsEPICOLON studyCancerOriginal guidelinesGene carriersRegression analysisGuidelinesTerms of sensitivity
2005
Differential Features of Colorectal Cancers Fulfilling Amsterdam Criteria without Involvement of the Mutator Pathway
Llor X, Pons E, Xicola RM, Castells A, Alenda C, Piñol V, Andreu M, Castellví-Bel S, Payá A, Jover R, Bessa X, Girós A, Roca A, Gassull MA, Association F. Differential Features of Colorectal Cancers Fulfilling Amsterdam Criteria without Involvement of the Mutator Pathway. Clinical Cancer Research 2005, 11: 7304-7310. PMID: 16243801, DOI: 10.1158/1078-0432.ccr-05-0965.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAgedAged, 80 and overCarrier ProteinsCohort StudiesColorectal NeoplasmsColorectal Neoplasms, Hereditary NonpolyposisDNA Mutational AnalysisDNA-Binding ProteinsFemaleGerm-Line MutationHumansImmunohistochemistryMaleMicrosatellite RepeatsMiddle AgedMutationMutL Protein Homolog 1MutS Homolog 2 ProteinNuclear ProteinsProspective StudiesSpainConceptsHereditary nonpolyposis colorectal cancerHNPCC patientsAmsterdam criteriaColorectal cancerPathway alterationsMicrosatellite instabilityMetachronous adenomatous polypsLeft-sided tumorsMismatch repair gene mutationsAmsterdam II criteriaColorectal cancer patientsNonpolyposis colorectal cancerRepair gene mutationsMismatch repair deficiencyDetailed family historyMMR alterationsEndometrial cancerLymphocytic infiltratePathologic dataCancer patientsFamily historyAdenomatous polypsHNPCC familiesPatientsTumor DNA