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
2019
Implication of DNA repair genes in Lynch-like syndrome
Xicola RM, Clark JR, Carroll T, Alvikas J, Marwaha P, Regan MR, Lopez-Giraldez F, Choi J, Emmadi R, Alagiozian-Angelova V, Kupfer SS, Ellis NA, Llor X. Implication of DNA repair genes in Lynch-like syndrome. Familial Cancer 2019, 18: 331-342. PMID: 30989425, PMCID: PMC6561810, DOI: 10.1007/s10689-019-00128-6.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overColorectal Neoplasms, Hereditary NonpolyposisDNA MethylationDNA Mismatch RepairDNA-Binding ProteinsFemaleGerm-Line MutationHeterozygoteHumansMaleMicrosatellite InstabilityMiddle AgedMismatch Repair Endonuclease PMS2MutL Protein Homolog 1MutS Homolog 2 ProteinSequence Analysis, DNAConceptsLLS patientsDistinct mutational signaturesGenome integrityLynch syndromeMutational signaturesMicrosatellite instabilityGermline mutationsColorectal cancerSequence analysisRepair genesSomatic MMR gene mutationsLS casesConsecutive CRC patientsMutational profileSomatic mutationsLynch-like syndromeL mutationMMR gene mutationsDNA repair genesFirst-degree relativesLikely pathogenic variantsSingle nucleotide variantsMLH1 promoter methylationTumor mutational profileExhibit microsatellite instability
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