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dc.contributor.authorZhang, P.
dc.contributor.authorHuang, Y.
dc.date.accessioned2021-04-12T16:16:38Z
dc.date.available2021-04-12T16:16:38Z
dc.date.issued2021-03-02
dc.identifier.urihttp://hdl.handle.net/10713/15160
dc.description.abstractImmune checkpoint therapy (ICT) can produce durable antitumor responses in various cancer types; however, the responses are not universal, and the predictive biomarkers are urgently needed. Growing evidence points to a link between epigenetic regulation and anti-tumor immunity, while clinical data on the association of genomic alterations in transcriptional dysregulation-related genes and ICT clinical benefit are lacking. Histone-lysine N-methyltransferase 2 (KMT2) family proteins methylate lysine 4 on the histone H3 tail at important regulatory regions in the genome and thereby impart crucial functions through modulating chromatin structures and DNA accessibility, which is associated with tumorigenesis, mutagenesis, and immune tolerance in various cancers, indicating its possible correlation with the output of immune checkpoint therapy. We hypothesized that genomic mutations in the KMT2 family have the potential to be a novel predictor of immunotherapeutic efficacy. Through integrative cancer genomic analyses of baseline tumor tissues from multiple cohorts involving immunotherapeutic patients, we uncovered a remarkable correlation between KMT2 family mutation and better immune checkpoint therapy responses in multiple patient cohorts. Then, we gathered all the independent ICT-treated datasets as a combination cohort consisted of 418 patients. Significant enrichment of KMT2 family genomic alterations in responding tumors was observed (odds ratio = 2.60, P value = 1.67e-04). This work distinguished the mutations in the KMT2 family as a potential predictor of favorable ICT response in multiple cancers, highlighting the importance of genomic profiling in immunotherapy. Copyright 2021, The Author(s).en_US
dc.description.urihttps://doi.org/10.1186/s13045-021-01050-0en_US
dc.language.isoen_USen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofJournal of Hematology and Oncology
dc.subjectBiomarkeren_US
dc.subjectImmune checkpoint therapyen_US
dc.subjectKMT2 gene familyen_US
dc.subjectLung canceren_US
dc.subjectMelanomaen_US
dc.titleGenomic alterations in KMT2 family predict outcome of immune checkpoint therapy in multiple cancersen_US
dc.typeArticleen_US
dc.identifier.doi10.1186/s13045-021-01050-0
dc.identifier.pmid33653367


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