Molecular refinement of pilocytic astrocytoma in adult patients.

IF 4 2区医学 Q1 CLINICAL NEUROLOGY

Neuropathology and Applied Neurobiology Pub Date : 2023-12-19 DOI:10.1111/nan.12949

Helena Bode, Catena Kresbach, Dörthe Holdhof, Mario M Dorostkar, Patrick N Harter, Jürgen Hench, Stephan Frank, Abigail K Suwala, Leonille Schweizer, Alicia Eckhardt, Sina Neyazi, Michael Bockmayr, Annika K Wefers, Ulrich Schüller

{"title":"Molecular refinement of pilocytic astrocytoma in adult patients.","authors":"Helena Bode, Catena Kresbach, Dörthe Holdhof, Mario M Dorostkar, Patrick N Harter, Jürgen Hench, Stephan Frank, Abigail K Suwala, Leonille Schweizer, Alicia Eckhardt, Sina Neyazi, Michael Bockmayr, Annika K Wefers, Ulrich Schüller","doi":"10.1111/nan.12949","DOIUrl":null,"url":null,"abstract":"Aim: Pilocytic astrocytomas (PA) in adults are rare and may be challenging to identify based only on histomorphology. Compared to their paediatric counterparts, they are reportedly molecularly more diverse and associated with a worse prognosis. We aimed to describe the characteristics of adult PAs more precisely by comprehensively profiling a series of 79 histologically diagnosed adult cases (≥18 years).Methods: We performed global DNA methylation profiling and DNA and RNA panel sequencing, and integrated the results with clinical data. We further compared the molecular characteristics of adult and paediatric PAs that had a significant match to one of the established PA methylation classes in the Heidelberg brain tumour classifier.Results: The mean age in our cohort was 33 years, and 43% of the tumours were located supratentorially. Based on methylation profiling, only 39% of the cases received a significant match to a PA methylation class. Sixteen per cent matched a different tumour type and 45% had a Heidelberg classifier score <0.9 with an affiliation to diverse established methylation classes in t-SNE analyses. Although the KIAA1549::BRAF fusion was found in 98% of paediatric PAs, this was true for only 27% of histologically defined and 55% of adult PAs defined by methylation profiling.Conclusions: A particularly high fraction of adult tumours with histological features of PA do not match current PA methylation classes, indicating ambiguous histology and an urgent need for molecular profiling. Moreover, even in adult PAs with a match to a PA methylation class, the distribution of genetic drivers differs significantly from their paediatric counterparts (p<0.01).","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":" ","pages":"e12949"},"PeriodicalIF":4.0000,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuropathology and Applied Neurobiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/nan.12949","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Aim: Pilocytic astrocytomas (PA) in adults are rare and may be challenging to identify based only on histomorphology. Compared to their paediatric counterparts, they are reportedly molecularly more diverse and associated with a worse prognosis. We aimed to describe the characteristics of adult PAs more precisely by comprehensively profiling a series of 79 histologically diagnosed adult cases (≥18 years).

Methods: We performed global DNA methylation profiling and DNA and RNA panel sequencing, and integrated the results with clinical data. We further compared the molecular characteristics of adult and paediatric PAs that had a significant match to one of the established PA methylation classes in the Heidelberg brain tumour classifier.

Results: The mean age in our cohort was 33 years, and 43% of the tumours were located supratentorially. Based on methylation profiling, only 39% of the cases received a significant match to a PA methylation class. Sixteen per cent matched a different tumour type and 45% had a Heidelberg classifier score <0.9 with an affiliation to diverse established methylation classes in t-SNE analyses. Although the KIAA1549::BRAF fusion was found in 98% of paediatric PAs, this was true for only 27% of histologically defined and 55% of adult PAs defined by methylation profiling.

Conclusions: A particularly high fraction of adult tumours with histological features of PA do not match current PA methylation classes, indicating ambiguous histology and an urgent need for molecular profiling. Moreover, even in adult PAs with a match to a PA methylation class, the distribution of genetic drivers differs significantly from their paediatric counterparts (p<0.01).

查看原文本刊更多论文

对成年患者中的朝粒细胞星形细胞瘤进行分子细化。

目的：成人嗜酸性粒细胞星形细胞瘤（PA）非常罕见，仅凭组织形态学很难鉴别。据报道，与儿科肿瘤相比，成人嗜酸性粒细胞星形细胞瘤的分子更多样化，预后更差。我们的目的是通过对79例经组织学诊断的成人病例（≥18岁）进行全面分析，更准确地描述成人PA的特征：我们进行了全局 DNA 甲基化分析以及 DNA 和 RNA 面板测序，并将结果与临床数据进行了整合。我们进一步比较了与海德堡脑肿瘤分类中已确立的 PA 甲基化类别之一显著匹配的成人和儿童 PA 的分子特征：我们队列中的平均年龄为 33 岁，43% 的肿瘤位于幕上。根据甲基化分析，只有39%的病例与PA甲基化类别显著匹配。16%的病例与不同的肿瘤类型相匹配，45%的病例得到了海德堡分类评分结论：具有 PA 组织学特征的成人肿瘤中有很大一部分与目前的 PA 甲基化分类不匹配，这表明组织学特征不明确，急需进行分子剖析。此外，即使在与 PA 甲基化分类相匹配的成人 PA 中，遗传驱动因素的分布也与儿科肿瘤有显著差异（P＜0.05）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Neuropathology and Applied Neurobiology 医学-病理学

CiteScore

8.20

自引率

2.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Neuropathology and Applied Neurobiology is an international journal for the publication of original papers, both clinical and experimental, on problems and pathological processes in neuropathology and muscle disease. Established in 1974, this reputable and well respected journal is an international journal sponsored by the British Neuropathological Society, one of the world leading societies for Neuropathology, pioneering research and scientific endeavour with a global membership base. Additionally members of the British Neuropathological Society get 50% off the cost of print colour on acceptance of their article.