{"doi":"10.3390/cancers13236092","title":"Tumor Mutation Burden, Expressed Neoantigens and the Immune Microenvironment in Diffuse Gliomas","abstract":"Background: A consistent correlation between tumor mutation burden (TMB) and tumor immune microenvironment has not been observed in gliomas as in other cancers. Methods: Driver germline and somatic mutations, TMB, neoantigen, and immune cell signatures were analyzed using whole exome sequencing (WES) and transcriptome sequencing of tumor and WES of matched germline DNA in a cohort of 66 glioma samples (44 IDH-mutant and 22 IDH-wildtype). Results: Fourteen samples revealed a hypermutator phenotype (HMP). Eight pathogenic (P) or likely pathogenic (LP) germline variants were detected in 9 (19%) patients. Six of these 8 genes were DNA damage repair genes. P/LP germline variants were found in 22% of IDH-mutant gliomas and 12.5% of IDH-wildtype gliomas (p = 0.7). TMB was correlated with expressed neoantigen but showed an inverse correlation with immune score (R = −0.46, p = 0.03) in IDH-wildtype tumors and no correlation in IDH-mutant tumors. The Antigen Processing and Presentation (APP) score correlated with immune score and was surprisingly higher in NHMP versus HMP samples in IDH-wildtype gliomas, but higher in HMP versus NHMP in IDH-mutant gliomas. Conclusion: TMB was inversely correlated with immune score in IDH-wildtype gliomas and showed no correlation in IDH-mutant tumors. APP was correlated with immune score and may be further investigated as a biomarker for response to immunotherapy in gliomas. Studies of germline variants in a larger glioma cohort are warranted.","journal":"Cancers","year":2021,"id":166469,"datarank":0.5333022092234121,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"self_citation_contribution":0.5333022092234121,"citation_network_contribution":0.0,"self_endowment_contribution":0.5333022092234121,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":336429,"name":"Ying Pang","orcid":"0000-0001-6195-2150","position":1,"is_corresponding":false},{"id":660012,"name":"Mythili Merchant","orcid":"0000-0002-2061-1306","position":2,"is_corresponding":false},{"id":482868,"name":"Chimene Kesserwan","orcid":"0000-0001-6043-2065","position":3,"is_corresponding":false},{"id":510888,"name":"Vineela Gangalapudi","orcid":null,"position":4,"is_corresponding":false},{"id":425135,"name":"Abdalla Abdelmaksoud","orcid":null,"position":5,"is_corresponding":false},{"id":660013,"name":"Alice Ranjan","orcid":"0000-0003-4746-0170","position":6,"is_corresponding":false},{"id":660014,"name":"Olga Kim","orcid":"0000-0002-4437-5870","position":7,"is_corresponding":false},{"id":250438,"name":"Jun S. 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