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High-confidence HLA genotyping of 576 children, adolescents, and young adults with recurrent or refractory disease used whole exome and RNA sequencing from MOSCATO-01 and MAPPYACTS. No reduced HLA allelic diversity emerged, but tumors showed discordant homozygosity and allele-frequency differences by histology. Somatic mutations in HLA and antigen processing genes were rare, except with mismatch repair deficiency or genetic instability. LOH prevalence varied across HLA classes, with marked increases in osteosarcoma, glioblastoma, Ewing sarcoma, and low-grade glioma, alongside heterogeneous HLA class I expression linked to HLA-B and TAP transcriptional 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was HLA status evaluated in the pediatric cohort?","Question",{"text":63,"@type":64},"High-confidence HLA genotypes were determined in 576 children, adolescents, and young adults using whole exome and RNA sequencing data and benchmarked algorithms from MOSCATO-01 and MAPPYACTS trials.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Did the study find a reduced HLA allelic diversity in pediatric solid cancers?",{"text":68,"@type":64},"No evidence for narrowed HLA allelic diversity was reported, though discordant homozygosity and allele frequencies differed across tumor types and subtypes.",{"name":70,"@type":61,"acceptedAnswer":71},"What mechanism commonly linked HLA class I loss in advanced pediatric solid tumors?",{"text":72,"@type":64},"HLA class I loss was commonly associated with transcriptional downregulation of HLA-B and transporter associated with antigen processing (TAP) 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10.3389/fimmu.2023.1265469  \nOPEN ACCESS  \nEDITED BY  \nManeesh K. Misra,  \nUniversity of Chicago Medicine, United States  \nREVIEWED BY Chang Liu,  \nWashington University in St. Louis, United States  \nBing Melody Zhang,  \nStanford University, United States  \n*CORRESPONDENCE Jerome Salmon  \n[jerome.salmon@gustaveroussy.fr](jerome.salmon@gustaveroussy.fr)[ ](jerome.salmon@gustaveroussy.fr)Birgit Geoerger  \n [birgit.geoerger@gustaveroussy.fr](birgit.geoerger@gustaveroussy.fr)[ ](birgit.geoerger@gustaveroussy.fr)†The authors supervised jointly  \nRECEIVED 22 July 2023  \nACCEPTED 06 November 2023  \nPUBLISHED 22 January 2024  \nCITATION  \nLim WC, Marques Da Costa ME, Godefroy K, Jacquet E, Gragert L, Rondof W, Marchais A, Nhiri N, Dalfovo D, Viard M, Labaied N, Khan AM, Dessen P, Romanel A, Pasqualini C, Schleiermacher G, Carrington M, Zitvogel L, Scoazec J-Y, Geoerger B and Salmon J (2024) Divergent HLA variations and heterogeneous expression but recurrent HLA loss-of-heterozygosity and common HLA-B and TAP transcriptional  \nsilencing across advanced pediatric solid cancers.  \nFront. Immunol. 14:1265469 .  \ndoi: 10.3389/fimmu.2023.1265469  \nCOPYRIGHT  \n© 2024 Lim, Marques Da Costa, Godefroy, Jacquet, Gragert, Rondof, Marchais, Nhiri, Dalfovo, Viard, Labaied, Khan, Dessen, Romanel, Pasqualini, Schleiermacher, Carrington, Zitvogel, Scoazec, Geoerger and Salmon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nDivergent HLA variations and heterogeneous expression but recurrent HLA loss-ofheterozygosity and common HLA-B and TAP transcriptional silencing across advanced pediatric solid cancers  \nWan Ching Lim 1,2,3, Maria Eugenia Marques Da Costa 1, Karine Godefroy4, Eric Jacquet 5, Loren Gragert 6, Windy Rondof 1,2, Antonin Marchais 1,2, Naima Nhiri 5,  \nDavide Dalfovo 7, Mathias Viard 8,9, Nizar Labaied 4, Asif M. Khan 3, Philippe Dessen 2, Alessandro Romanel 7, Claudia Pasqualini 1,10,  \nGudrun Schleiermacher 11, Mary Carrington 8,9,12, Laurence Zitvogel 1, Jean-Yves Scoazec 4, Birgit Geoerger 1,10*† and Jerome Salmon 1*†  \n1 INSERM U1015, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France,  \n2 Bioinformatics Platform, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France, 3School of Data Sciences, Perdana University, Kuala Lumpur, Malaysia, 4 Department of Pathology and Laboratory Medicine, Translational Research Laboratory and Biobank, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France, 5 Institut de Chimie des Substances Naturelles, CNRS UPR2301, Universite´ Paris-Saclay, Gif-sur-Yvette, France, 6 Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, United States, 7 Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy, 8 Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, United States,  \n9 Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States, 10 Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France, 11 INSERM U830, Recherche Translationnelle en Oncologie Pe´ diatrique (RTOP), and SIREDO Oncology Center (Care, Innovation and Research for Children and AYA with Cancer), PSL Research University, Institut Curie, Paris, France, 12 Ragon Institute of Massachusetts General Hospit","cbCaioF5Y4bD82k9","https://ap.wps.com/l/cbCaioF5Y4bD82k9","pdf",9569148,25,"English","# HLA variation and expression in pediatric solid tumors\n## Study design and cohort\n## HLA allele diversity and genotype patterns\n## Somatic mutations in HLA and antigen processing genes\n## LOH prevalence across cancer types\n## HLA antigen expression and transcriptional mechanisms","[{\"question\":\"How was HLA status evaluated in the pediatric cohort?\",\"answer\":\"High-confidence HLA genotypes were determined in 576 children, adolescents, and young adults using whole exome and RNA sequencing data and benchmarked algorithms from MOSCATO-01 and MAPPYACTS trials.\"},{\"question\":\"Did the study find a reduced HLA allelic diversity in pediatric solid cancers?\",\"answer\":\"No evidence for narrowed HLA allelic diversity was reported, though discordant homozygosity and allele frequencies differed across tumor types and subtypes.\"},{\"question\":\"What mechanism commonly linked HLA class I loss in advanced pediatric solid tumors?\",\"answer\":\"HLA class I loss was commonly associated with transcriptional downregulation of HLA-B and transporter associated with antigen processing (TAP) genes.\"}]","Divergent HLA variations and heterogeneous expression but recurrent HLA loss-of-heterozygosity and common HLA-B and TAP transcriptional silencing across advanced pediatric solid cancers | PDF",1790019180,63]