{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:53:14Z","timestamp":1791280394214,"version":"4.1.0"},"posted":{"date-parts":[[2026,10,2]]},"group-title":"Cancer Biology","reference-count":62,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health"},{"name":"National Institutes of Health","award":["K22 CA258953"],"award-info":[{"award-number":["K22 CA258953"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Neuronal-cancer cell interactions are a key component of brain tumor pathophysiology, yet many fundamental questions remain unanswered \u2013 with even more remaining unasked. Here, we present a comprehensive brain tumor reference map generated from bulk RNA-seq data of \u223c4,300 adult and pediatric brain tumors\u2014including various glioma subtypes, medulloblastomas, ependymomas, and meningiomas\u2014alongside \u223c1,400 healthy brain samples. By analyzing synaptic processes and synaptic gene expression across tumor types, we reveal the complexity of neuron-tumor crosstalk and its potential impact on patient survival. Our findings identify key synaptic signaling pathways and dysregulated patterns in brain tumors, including\n                  <jats:italic>HNRNPH2<\/jats:italic>\n                  upregulation, a key factor in RNA processing and metabolism, in gliomas and medulloblastomas. Additionally, we highlight the role of cholinergic signaling, particularly\n                  <jats:italic>CHRNA9<\/jats:italic>\n                  , as a driver of glioma progression, which is also upregulated in WNT and Group 4 medulloblastomas, ependymomas, and meningiomas. Furthermore, P2 purinergic signaling emerges as a key player in glioma progression. These insights lay the groundwork for future studies exploring whether targeting these pathways could reprogram the tumor microenvironment toward an anti-tumor state, ultimately leading to novel therapeutic strategies and improved patient outcomes.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>\n                        A comprehensive\n                        <jats:bold>brain tumor reference map<\/jats:bold>\n                        was generated using bulk RNA-seq from \u223c4,300 adult and pediatric brain tumors and \u223c1,400 healthy brain samples.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        <jats:bold>\n                          <jats:italic>HNRNPH2<\/jats:italic>\n                        <\/jats:bold>\n                        is consistently upregulated across all adult and pediatric gliomas, as well as all medulloblastoma subgroups.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        <jats:bold>Nicotinic acetylcholine receptors (nAChRs)<\/jats:bold>\n                        are upregulated in glioblastomas and pediatric high-grade gliomas but downregulated in low-grade gliomas, underscoring their role in glioma aggressiveness.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        <jats:bold>\n                          <jats:italic>CHRNA9<\/jats:italic>\n                        <\/jats:bold>\n                        is a key driver of glioma progression and is also upregulated in medulloblastomas (WNT and Group 4), ependymomas, and meningiomas\n                      <\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"755821v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.30.755821","type":"posted-content","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:10:11Z","timestamp":1790932211000},"source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic analysis reveals differential regulation of synaptic components in pediatric and adult brain tumors"],"prefix":"10.64898","author":[{"given":"Leyre","family":"Merino-Galan","sequence":"first","affiliation":[{"name":"Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children\u2019s Research Institute, Seattle, WA, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6661-3024","authenticated-orcid":false,"given":"Sonali","family":"Arora","sequence":"additional","affiliation":[{"name":"Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Glatzer","sequence":"additional","affiliation":[{"name":"Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Jensen","sequence":"additional","affiliation":[{"name":"Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1300-0774","authenticated-orcid":false,"given":"Ashmitha","family":"Rajendran","sequence":"additional","affiliation":[{"name":"Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children\u2019s Research Institute, Seattle, WA, United States of America"},{"name":"Department of Biomedical Informatics and Education, University of Washington, Seattle, WA, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C.","family":"Holland","sequence":"additional","affiliation":[{"name":"Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4434-3139","authenticated-orcid":false,"given":"Siobhan 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