{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:50:17Z","timestamp":1747183817269,"version":"3.40.5"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T00:00:00Z","timestamp":1722816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202983"],"award-info":[{"award-number":["82202983"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study investigated the role of O<jats:sup>6<\/jats:sup>\u2010methylguanine\u2010DNA methyltransferase promoter (MGMTp) methylation hierarchy and heterogeneity in grade 2\u20133 gliomas, focusing on variations in chemotherapy benefits and resection dependency. A cohort of 668 newly diagnosed grade 2\u20133 gliomas, with comprehensive clinical, radiological, and molecular data, formed the basis of this analysis. The extent of resection was categorized into gross total resection (GTR \u2265100%), subtotal resection (STR &gt;90%), and partial resection (PR \u226490%). MGMTp methylation levels were examined using quantitative pyrosequencing. Our findings highlighted the critical role of GTR in improving the prognosis for astrocytomas (IDH1\/2\u2010mutant and 1p\/19q non\u2010codeleted), contrasting with its lesser significance for oligodendrogliomas (IDH1\/2 mutation and 1p\/19q codeletion). Oligodendrogliomas demonstrated the highest average MGMTp methylation levels (median: 28%), with a predominant percentage of methylated cases (average methylation levels &gt;20%). Astrocytomas were more common in the low\u2010methylated group (10%\u201320%), while IDH wild\u2010type gliomas were mostly unmethylated (&lt;10%). Spatial distribution analysis revealed a decrement in frontal lobe involvement from methylated, low\u2010methylated to unmethylated cases (72.8%, 59.3%, and 47.8%, respectively). In contrast, low\u2010methylated and unmethylated cases were more likely to invade the temporal\u2010insular region (19.7%, 34.3%, and 40.4%, respectively). Astrocytomas with intermediate MGMTp methylation were notably associated with temporal\u2010insular involvement, potentially indicating a moderate response to temozolomide and underscoring the importance of aggressive resection strategies. In conclusion, our study elucidates the complex interplay of MGMTp methylation hierarchy and heterogeneity among grade 2\u20133 gliomas, providing insights into why astrocytomas and IDH wild\u2010type lower\u2010grade glioma might derive less benefit from chemotherapy.<\/jats:p>","DOI":"10.1111\/cas.16268","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T14:29:23Z","timestamp":1722868163000},"page":"3403-3414","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unveiling hierarchy and spatial distribution of O<sup>6<\/sup>\u2010methylguanine\u2010DNA methyltransferase promoter methylation in World Health Organization grade 2\u20133 gliomas"],"prefix":"10.1111","volume":"115","author":[{"given":"Mingxiao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurosurgery China\u2010Japan Friendship Hospital  Beijing China"},{"name":"Department of Neurosurgical 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