Hia S Ghosh, Ruchit V Patel, Elizabeth B Claus, L Nicolas Gonzalez Castro, Patrick Y Wen, Keith L Ligon, David M Meredith, Wenya Linda Bi
{"title":"典型扩增和 CDKN2A/B 缺失细化了 IDH1/2 突变星形细胞瘤的预后。","authors":"Hia S Ghosh, Ruchit V Patel, Elizabeth B Claus, L Nicolas Gonzalez Castro, Patrick Y Wen, Keith L Ligon, David M Meredith, Wenya Linda Bi","doi":"10.1093/neuonc/noae258","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Molecular features have been incorporated alongside histologic criteria to improve glioma diagnostics and prognostication. CDKN2A/B homozygous-loss associates with worse survival in IDH1/2-mutant astrocytomas (IDHmut-astrocytomas), the presence of which denotes grade 4 tumor independent of histologic features. However, no molecular features distinguish survival amongst histologically-defined grade 2 and 3 IDHmut-astrocytomas.</p><p><strong>Methods: </strong>We assembled a cohort of patients ≥19 years old diagnosed with an IDHmut-astrocytoma between 1989-2020 from public datasets and several academic medical centers. Multivariate modeling and unbiased clustering were used to stratify risk.</p><p><strong>Results: </strong>We identified 998 IDHmut-astrocytoma patients (41.5% female; 85.6% white). Tumor grade, CDKN2A/B loss, and/or ≥1 focal amplification was associated with reduced survival. Grade 2/3 patients with intact CDKN2A/B and no focal amplifications survived the longest (OS 205.7 months). Survival for grade 2/3 cases with either CDKN2A/B hemizygous-loss or focal amplifications (80.4, 88.7 months respectively) did not differ significantly from grade 4 cases with intact CDKN2A/B and no amplifications (91.5 months, p=0.93). Grade 4 patients with either hemizygous or homozygous loss of CDKN2A/B had the shortest survival (OS 31.9, 32.5 months respectively), followed by grade 4 cases with intact CDKN2A/B and focal gene amplifications (OS 55.9 months). Integrating CDKN2A/B status and amplifications alongside histopathologic grade refined overall survival prediction. Unbiased clustering revealed 9 distinct molecular profiles, with differential survival. IDHmut-astrocytomas with any CDKN2A/B-loss clustered together, regardless of grade, and exhibited the poorest outcomes.</p><p><strong>Conclusions: </strong>Combining CDKN2A/B hemizygous-loss and focal gene amplifications reveals a group of IDHmut-astrocytoma patients with intermediate prognosis, refining IDHmut-astrocytoma classification.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4000,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Canonical Amplifications and CDKN2A/B Loss Refine IDH1/2-mutant Astrocytoma Prognosis.\",\"authors\":\"Hia S Ghosh, Ruchit V Patel, Elizabeth B Claus, L Nicolas Gonzalez Castro, Patrick Y Wen, Keith L Ligon, David M Meredith, Wenya Linda Bi\",\"doi\":\"10.1093/neuonc/noae258\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Molecular features have been incorporated alongside histologic criteria to improve glioma diagnostics and prognostication. CDKN2A/B homozygous-loss associates with worse survival in IDH1/2-mutant astrocytomas (IDHmut-astrocytomas), the presence of which denotes grade 4 tumor independent of histologic features. However, no molecular features distinguish survival amongst histologically-defined grade 2 and 3 IDHmut-astrocytomas.</p><p><strong>Methods: </strong>We assembled a cohort of patients ≥19 years old diagnosed with an IDHmut-astrocytoma between 1989-2020 from public datasets and several academic medical centers. Multivariate modeling and unbiased clustering were used to stratify risk.</p><p><strong>Results: </strong>We identified 998 IDHmut-astrocytoma patients (41.5% female; 85.6% white). Tumor grade, CDKN2A/B loss, and/or ≥1 focal amplification was associated with reduced survival. Grade 2/3 patients with intact CDKN2A/B and no focal amplifications survived the longest (OS 205.7 months). Survival for grade 2/3 cases with either CDKN2A/B hemizygous-loss or focal amplifications (80.4, 88.7 months respectively) did not differ significantly from grade 4 cases with intact CDKN2A/B and no amplifications (91.5 months, p=0.93). Grade 4 patients with either hemizygous or homozygous loss of CDKN2A/B had the shortest survival (OS 31.9, 32.5 months respectively), followed by grade 4 cases with intact CDKN2A/B and focal gene amplifications (OS 55.9 months). Integrating CDKN2A/B status and amplifications alongside histopathologic grade refined overall survival prediction. Unbiased clustering revealed 9 distinct molecular profiles, with differential survival. IDHmut-astrocytomas with any CDKN2A/B-loss clustered together, regardless of grade, and exhibited the poorest outcomes.</p><p><strong>Conclusions: </strong>Combining CDKN2A/B hemizygous-loss and focal gene amplifications reveals a group of IDHmut-astrocytoma patients with intermediate prognosis, refining IDHmut-astrocytoma classification.</p>\",\"PeriodicalId\":19377,\"journal\":{\"name\":\"Neuro-oncology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":16.4000,\"publicationDate\":\"2024-11-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuro-oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/neuonc/noae258\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuro-oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/neuonc/noae258","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Canonical Amplifications and CDKN2A/B Loss Refine IDH1/2-mutant Astrocytoma Prognosis.
Background: Molecular features have been incorporated alongside histologic criteria to improve glioma diagnostics and prognostication. CDKN2A/B homozygous-loss associates with worse survival in IDH1/2-mutant astrocytomas (IDHmut-astrocytomas), the presence of which denotes grade 4 tumor independent of histologic features. However, no molecular features distinguish survival amongst histologically-defined grade 2 and 3 IDHmut-astrocytomas.
Methods: We assembled a cohort of patients ≥19 years old diagnosed with an IDHmut-astrocytoma between 1989-2020 from public datasets and several academic medical centers. Multivariate modeling and unbiased clustering were used to stratify risk.
Results: We identified 998 IDHmut-astrocytoma patients (41.5% female; 85.6% white). Tumor grade, CDKN2A/B loss, and/or ≥1 focal amplification was associated with reduced survival. Grade 2/3 patients with intact CDKN2A/B and no focal amplifications survived the longest (OS 205.7 months). Survival for grade 2/3 cases with either CDKN2A/B hemizygous-loss or focal amplifications (80.4, 88.7 months respectively) did not differ significantly from grade 4 cases with intact CDKN2A/B and no amplifications (91.5 months, p=0.93). Grade 4 patients with either hemizygous or homozygous loss of CDKN2A/B had the shortest survival (OS 31.9, 32.5 months respectively), followed by grade 4 cases with intact CDKN2A/B and focal gene amplifications (OS 55.9 months). Integrating CDKN2A/B status and amplifications alongside histopathologic grade refined overall survival prediction. Unbiased clustering revealed 9 distinct molecular profiles, with differential survival. IDHmut-astrocytomas with any CDKN2A/B-loss clustered together, regardless of grade, and exhibited the poorest outcomes.
Conclusions: Combining CDKN2A/B hemizygous-loss and focal gene amplifications reveals a group of IDHmut-astrocytoma patients with intermediate prognosis, refining IDHmut-astrocytoma classification.
期刊介绍：
Neuro-Oncology, the official journal of the Society for Neuro-Oncology, has been published monthly since January 2010. Affiliated with the Japan Society for Neuro-Oncology and the European Association of Neuro-Oncology, it is a global leader in the field.
The journal is committed to swiftly disseminating high-quality information across all areas of neuro-oncology. It features peer-reviewed articles, reviews, symposia on various topics, abstracts from annual meetings, and updates from neuro-oncology societies worldwide.
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