2025
High MGMT expression identifies aggressive colorectal cancer with distinct genomic features and immune evasion properties
Zhang J, Rajendran B, Desai S, Gibson J, DiPalermo J, LoRusso P, Kong Y, Zhao H, Cecchini M, Schalper K. High MGMT expression identifies aggressive colorectal cancer with distinct genomic features and immune evasion properties. Journal For ImmunoTherapy Of Cancer 2025, 13: e011653. PMID: 40935566, DOI: 10.1136/jitc-2025-011653.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesCD8+ tumor-infiltrating lymphocytesPromoter methylation statusMGMT expressionMGMT overexpressionClinical significanceAllogeneic peripheral blood mononuclear cellsCD8+ T cellsMGMT promoter methylation statusKilling of malignant cellsMGMT-expressing cellsMultiplexed quantitative immunofluorescencePeripheral blood mononuclear cellsAggressive clinical courseMGMT protein expressionAggressive colorectal cancerMethylation statusExpression of MGMTLevels of MGMT proteinMGMT protein levelsImmune evasion propertiesBlood mononuclear cellsMutational featuresAdaptive immune evasionSomatic mutation burden
2024
Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
Chen Z, Guo X, Tao R, Huyghe J, Law P, Fernandez-Rozadilla C, Ping J, Jia G, Long J, Li C, Shen Q, Xie Y, Timofeeva M, Thomas M, Schmit S, Díez-Obrero V, Devall M, Moratalla-Navarro F, Fernandez-Tajes J, Palles C, Sherwood K, Briggs S, Svinti V, Donnelly K, Farrington S, Blackmur J, Vaughan-Shaw P, Shu X, Lu Y, Broderick P, Studd J, Harrison T, Conti D, Schumacher F, Melas M, Rennert G, Obón-Santacana M, Martín-Sánchez V, Oh J, Kim J, Jee S, Jung K, Kweon S, Shin M, Shin A, Ahn Y, Kim D, Oze I, Wen W, Matsuo K, Matsuda K, Tanikawa C, Ren Z, Gao Y, Jia W, Hopper J, Jenkins M, Win A, Pai R, Figueiredo J, Haile R, Gallinger S, Woods M, Newcomb P, Duggan D, Cheadle J, Kaplan R, Kerr R, Kerr D, Kirac I, Böhm J, Mecklin J, Jousilahti P, Knekt P, Aaltonen L, Rissanen H, Pukkala E, Eriksson J, Cajuso T, Hänninen U, Kondelin J, Palin K, Tanskanen T, Renkonen-Sinisalo L, Männistö S, Albanes D, Weinstein S, Ruiz-Narvaez E, Palmer J, Buchanan D, Platz E, Visvanathan K, Ulrich C, Siegel E, Brezina S, Gsur A, Campbell P, Chang-Claude J, Hoffmeister M, Brenner H, Slattery M, Potter J, Tsilidis K, Schulze M, Gunter M, Murphy N, Castells A, Castellví-Bel S, Moreira L, Arndt V, Shcherbina A, Bishop D, Giles G, Southey M, Idos G, McDonnell K, Abu-Ful Z, Greenson J, Shulman K, Lejbkowicz F, Offit K, Su Y, Steinfelder R, Keku T, van Guelpen B, Hudson T, Hampel H, Pearlman R, Berndt S, Hayes R, Martinez M, Thomas S, Pharoah P, Larsson S, Yen Y, Lenz H, White E, Li L, Doheny K, Pugh E, Shelford T, Chan A, Cruz-Correa M, Lindblom A, Hunter D, Joshi A, Schafmayer C, Scacheri P, Kundaje A, Schoen R, Hampe J, Stadler Z, Vodicka P, Vodickova L, Vymetalkova V, Edlund C, Gauderman W, Shibata D, Toland A, Markowitz S, Kim A, Chanock S, van Duijnhoven F, Feskens E, Sakoda L, Gago-Dominguez M, Wolk A, Pardini B, FitzGerald L, Lee S, Ogino S, Bien S, Kooperberg C, Li C, Lin Y, Prentice R, Qu C, Bézieau S, Yamaji T, Sawada N, Iwasaki M, Le Marchand L, Wu A, Qu C, McNeil C, Coetzee G, Hayward C, Deary I, Harris S, Theodoratou E, Reid S, Walker M, Ooi L, Lau K, Zhao H, Hsu L, Cai Q, Dunlop M, Gruber S, Houlston R, Moreno V, Casey G, Peters U, Tomlinson I, Zheng W. Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes. Nature Communications 2024, 15: 3557. PMID: 38670944, PMCID: PMC11053150, DOI: 10.1038/s41467-024-47399-x.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesCredible causal variantsColorectal cancer susceptibility genesSusceptibility genesAssociation signalsAnalysis of single-cell RNA-seq dataAnalysis of whole-exome sequencing dataGenome-wide association study dataColorectal cancer risk lociSingle-cell RNA-seq dataTarget genesWhole-exome sequencing dataFunctional genomic investigationsFine-mapping analysisRNA-seq dataExome sequencing dataTissue-specific transcriptomesColorectal cancerCancer susceptibility genesCausal variantsFine-mappingRisk lociMethylome dataSequence dataGenomic investigations
2023
Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer
Cecchini M, Zhang J, Wei W, Sklar J, Lacy J, Zhong M, Kong Y, Zhao H, DiPalermo J, Devine L, Stein S, Kortmansky J, Johung K, Bindra R, LoRusso P, Schalper K. Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer. Cancer Research Communications 2023, 3: 1132-1139. PMID: 37387791, PMCID: PMC10305782, DOI: 10.1158/2767-9764.crc-23-0045.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingMGMT protein expressionColorectal cancerStable diseaseQuantitative immunofluorescenceT cellsProtein expressionPromoter hypermethylationLow MGMT protein expressionPARP inhibitorsRadiographic tumor regressionMetastatic colorectal cancerAdvanced colorectal cancerPretreatment tumor biopsiesEffector T cellsTumor-infiltrating lymphocytesMGMT proteinDNA repair biomarkersBaseline CD8Eligible patientsIncreased CD8Methylguanine-DNA methyltransferaseObjective responseProgressive diseaseImmune markers
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