{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:38:58Z","timestamp":1792737538987,"version":"4.5.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sanford Stem Cell Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mutations in the telomerase reverse transcriptase (TERT) promoter region (TPM), particularly C228T and C250T, are common in IDH-wildtype glioblastoma (GBM). The single nucleotide polymorphism (SNP) rs2853669, also located in the TERT promoter, may influence telomerase activity, though its clinical relevance in GBM remains unclear. This study examined the allelic configuration between rs2853669 and TPM to elucidate their combined effects on TERT expression and clinical outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Seventy-six TPM-positive GBM tumors from Japanese patients were analyzed by nested PCR, and patients were classified by rs2853669 genotype (T\/T, T\/C, C\/C). In the T\/C subgroup, the allelic configuration between the SNP and TPM was determined as cis (same allele) or trans (different alleles). Clinical data, TERT expression, and prognosis were compared among groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 76 patients, 37 (48.7%) had T\/T, 30 (39.5%) had T\/C, and 9 (11.8%) had C\/C genotypes. The rs2853669 C allele frequency was higher in GBM than in the general Japanese population (31.6% vs 24.5%, P\u2009=\u2009.047). Among T\/C cases, 53.3% showed a cis configuration. Patients carrying the SNP and TPM on the same allele (C\/C and T\/C cis) had shorter overall survival than those carrying them on different alleles (T\/T or T\/C trans; 19 vs 25 months, P\u2009=\u2009.048), and TERT expression was also lower in this group (P\u2009=\u2009.038).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The rs2853669 C allele may increase GBM susceptibility and, when in cis with TPM, is associated with reduced TERT expression and poorer prognosis, underscoring its biological and clinical significance in TPM-mutant GBM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noag237","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:27:19Z","timestamp":1790594839000},"source":"Crossref","is-referenced-by-count":0,"title":["SNP rs2853669 potentially elevates the risk of glioblastoma development and leads to worse prognosis when in cis with mutant telomerase reverse transcriptase promoter in a Japanese cohort"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7679-173X","authenticated-orcid":false,"given":"Daisuke","family":"Kawauchi","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California , San Diego, California,","place":["USA"]},{"name":"Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, (D.K., M.H.-K., Y.N.)","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7713-4419","authenticated-orcid":false,"given":"Yohei","family":"Miyake","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California , San Diego, California,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3962-6134","authenticated-orcid":false,"given":"Brett","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0877-5639","authenticated-orcid":false,"given":"Joseph","family":"Bendik","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California , San Diego, California,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9625-8668","authenticated-orcid":false,"given":"Shunichiro","family":"Miki","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Tsukuba Hospital, Tsukuba City, (S.M.)","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2147-4629","authenticated-orcid":false,"given":"Mai","family":"Honda-Kitahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6190-9304","authenticated-orcid":false,"given":"Jill","family":"Barnholtz-Sloan","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute, Emory University , Atlanta, Georgia,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0933-1714","authenticated-orcid":false,"given":"Tomoyuki","family":"Nakano","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Institute of Science Tokyo , Tokyo, (T.N.)","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5275-0548","authenticated-orcid":false,"given":"Philip","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California , San Diego, California,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3903-2662","authenticated-orcid":false,"given":"Raghavendra","family":"Vadla","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California , San Diego, California,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5790-0216","authenticated-orcid":false,"given":"Brandon M","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California , San Diego, California,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3036-0253","authenticated-orcid":false,"given":"Clark","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California , San Diego, California,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sejal","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California , San Diego, California,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4303-6006","authenticated-orcid":false,"given":"Yoshitaka","family":"Narita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1909-4361","authenticated-orcid":false,"given":"Frank","family":"Furnari","sequence":"additional","affiliation":[{"name":"Department 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