Brain Pathology最新文献

{"title":"A 23-year-old woman with a headache and imbalance.","authors":"Lukas Marcelis, Andrew Folpe, Sounak Gupta, Cinthya J Zepeda Mendoza","doi":"10.1111/bpa.70008","DOIUrl":"https://doi.org/10.1111/bpa.70008","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70008"},"PeriodicalIF":5.8,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Herpes simplex virus-1 infection alters microtubule-associated protein Tau splicing and promotes Tau pathology in neural models of Alzheimer's disease.","authors":"Emmanuel C Ijezie, Michael J Miller, Celine Hardy, Ava R Jarvis, Timothy F Czajka, Lianna D'Brant, Natasha Rugenstein, Adam Waickman, Eain Murphy, David C Butler","doi":"10.1111/bpa.70006","DOIUrl":"10.1111/bpa.70006","url":null,"abstract":"<p><p>Herpes simplex virus 1 (HSV-1) infection alters critical markers of Alzheimer's disease (AD) in neurons. One key marker of AD is the hyperphosphorylation of Tau, accompanied by altered levels of Tau isoforms. However, an imbalance in these Tau splice variants, specifically resulting from altered 3R to 4R MAPT splicing of exon 10, has yet to be directly associated with HSV-1 infection. To this end, we infected 2D and 3D human neural models with HSV-1 and monitored MAPT splicing and Tau phosphorylation. Further, we transduced SH-SY5Y neurons with HSV-1 ICP27, which alters RNA splicing, to analyze if ICP27 alone is sufficient to induce altered MAPT exon 10 splicing. We show that HSV-1 infection induces altered splicing of MAPT exon 10, increasing 4R-Tau protein levels, Tau hyperphosphorylation, and Tau oligomerization. Our experiments reveal a novel link between HSV-1 infection and the development of cytopathic phenotypes linked with AD progression.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70006"},"PeriodicalIF":5.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple intracranial hemorrhages in a postmenopausal female.","authors":"Xinhua Lu, Xinya Xu, Xiaopeng Zhang","doi":"10.1111/bpa.70007","DOIUrl":"https://doi.org/10.1111/bpa.70007","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70007"},"PeriodicalIF":5.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOCIETY NEWS","authors":"Audrey Rousseau","doi":"10.1111/bpa.70009","DOIUrl":"https://doi.org/10.1111/bpa.70009","url":null,"abstract":"&lt;p&gt;&lt;b&gt;The ISN is looking for a group of young motivated neuropathologists&lt;/b&gt; to promote the specialty via the ISN website. If you are interested in participating, please contact Audrey Rousseau (&lt;span&gt;[email protected]&lt;/span&gt;) or Monika Hofer (&lt;span&gt;[email protected]&lt;/span&gt;).&lt;/p&gt;&lt;p&gt;&lt;b&gt;The International Congress of Neuropathology (ICN)&lt;/b&gt; will be held in Edinburgh, Scotland, in 2027 (ICN27). The Congress President will be Prof Colin Smith and the ICN27 will be hosted by the British Neuropathological Society (BNS).&lt;/p&gt;&lt;p&gt;“On behalf of the British Neuropathological Society I am delighted to extend a warm invitation to all our colleagues across the world to join us in Edinburgh for the International Congress of Neuropathology 2027. Edinburgh is an easily accessible centre, surrounded by 1000 years of living history. We will develop a strong academic programme covering all aspects of neuropathology with world leading plenary speakers, supported by a social programme highlighting some of Edinburgh's historic charms. For those wishing to explore further, Edinburgh offers access to many of Scotland's highlights, be it touring the Highlands, sampling our famous whisky or golfing on some of our picturesque courses. I do hope you will be able to join us for what I am sure will be a memorable meeting showcasing the best in international neuropathology.&lt;/p&gt;&lt;p&gt;Colin Smith&lt;/p&gt;&lt;p&gt;Congress President ISN 2027”&lt;/p&gt;&lt;p&gt;Summary report for ICN23 Berlin (our most recent International Congress of Neuropathology, September 2023) now available in the Society's journal Brain Pathology (see link: https://doi.org/10.1111/bpa.13249).&lt;/p&gt;&lt;p&gt;We are delighted to start the bidding process for holding the &lt;b&gt;2031 XXII International Congress of Neuropathology (ICN)&lt;/b&gt;. As you know, the 2027 XXI ICN Congress will be in Edinburgh and we now need to think ahead to 2031 and find a new home for our much-loved congress.&lt;/p&gt;&lt;p&gt;The Invitation Letter calling for bids and outlining the process can be found on the ISN website (www.intsocneuropathol.com). Please note that the deadline is the &lt;b&gt;31st August 2025&lt;/b&gt;.&lt;/p&gt;&lt;p&gt;The &lt;b&gt;7th Quadrennial Meeting of the World Federation of Neuro-Oncology Societies&lt;/b&gt; will be held in conjunction with the 30th Annual Meeting &amp; Education Day of the Society for Neuro-Oncology &lt;b&gt;November 19-23, 2025&lt;/b&gt; in Honolulu, Hawaii.&lt;/p&gt;&lt;p&gt;&lt;b&gt;&lt;i&gt;Brain Pathology has joined Wiley's Open Access&lt;/i&gt;&lt;/b&gt; portfolio as of January 2021. As a result, all submissions are subject to an Article Publication Charge (APC) if accepted and published in the journal. ISN members are eligible for a 10% discount off the Open Access APC. For more information on the fees, please click here.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Free resource: digital microscopy platform for neurodegenerative diseases curated in Munich&lt;/b&gt;. Prof Jochen Herms and his team have been setting up a digital microscopy platform for neurodegenerative diseases in their department in Munich. Registration is free. ISN members and interested","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spliceosome protein alterations differentiate hubs of the default mode connectome during the progression of Alzheimer's disease.","authors":"Sylvia E Perez, Muhammad Nadeem, Bin He, Jennifer C Miguel, David G Moreno, Marta Moreno-Rodriguez, Michael Malek-Ahmadi, Chadwick M Hales, Elliott J Mufson","doi":"10.1111/bpa.70004","DOIUrl":"https://doi.org/10.1111/bpa.70004","url":null,"abstract":"<p><p>Default mode network (DMN) is comprised in part of the frontal (FC), precuneus (PreC), and posterior cingulate (PCC) cortex and displays amyloid and tau pathology in Alzheimer's disease (AD). The PreC hub appears the most resilient to AD pathology, suggesting differential vulnerability within the DMN. However, the mechanisms that underlie this differential pathobiology remain obscure. Here, we investigated changes in RNA polymerase II (RNA pol II) and splicing proteins U1-70K, U1A, SRSF2, and hnRNPA2B1, phosphorylated AT8 tau, 3R and 4Rtau isoforms containing neurons and amyloid plaques in layers III and V-VI in FC, PreC, and PCC obtained from individuals with a preclinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), and mild/moderate mAD. We found a significant increase in pS5-RNA pol II levels in FC NCI, U1-70K in PreC MCI and mAD, and hnRNPA2B1 and SRSF2 levels in PCC mAD. 1N3Rtau levels were significantly increased in FC, decreased in PreC in mAD, and unchanged in PCC, whereas 1N4Rtau increased in mAD across the hubs. SRSF2, U1-70K, U1A, and hnRNPA2B1 nuclear optical density (OD), size, and number were unchanged across groups in FC and PCC, while PreC OD hnRNPA2B1 was significantly greater in mAD. Mislocalized U1A and U1-70K tangle-like structures were found in a few PCC cases and colocalized with AT8-bearing neurofibrillary tangles (NFTs). FC pS5-RNA pol II, PreC U1-70K, Pre pS5,2-RNA pol II, and PCC hnRNPA2B1 and SRSF2 protein levels were associated with cognitive decline but not neuropathology across clinical groups. By contrast, splicing protein nuclear OD measures, size, counts, and mislocalized U1-70K and U1A NFT-like structures were not correlated with NFT or plaque density, cognitive domains, and neuropathological criteria in DMN hubs. Findings suggest that RNA splicing protein alterations and U1 mislocalization contribute differentially to DMN pathogenesis and cognitive deterioration in AD.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70004"},"PeriodicalIF":5.8,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraventricular mass in a 52-year-old woman","authors":"Felix Mircea Brehar,&nbsp;Alexandra Mihaela Pătrășcan,&nbsp;Mihaela Andreescu,&nbsp;Laura-Gabriela Țîrlea,&nbsp;Sabina-Loredana-Georgiana Olteanu,&nbsp;Simon Schallenberg,&nbsp;Mihnea P. Dragomir,&nbsp;George E. D. Petrescu","doi":"10.1111/bpa.70003","DOIUrl":"10.1111/bpa.70003","url":null,"abstract":"&lt;p&gt;A 52-year-old woman, without previous medical history, presented to our hospital with acute onset of headache, dizziness, and fatigability. Brain magnetic resonance imaging (MRI) revealed a 17.4 mm × 15.4 mm × 23.5 mm solitary, circumscribed, well-defined enhancing mass, centered on the trigone of the left lateral ventricle. Radiological findings were suggestive of intraventricular meningioma (Figure 1). The patient underwent surgery, and a gross total resection was performed. The intraoperative macroscopic findings were typical for a meningioma—the tumor was overly fibrous, well-defined, firm, encapsulated, and attached to the ventricular walls and choroid plexus.&lt;/p&gt;&lt;p&gt;Histological examination revealed a tumor composed of a mixture of diffuse infiltrates of medium-sized lymphocytes with rounded and angled nuclei and relatively abundant pale cytoplasm, and plasmacytoid cells with paracentric nuclei, wheel-like chromatin, and eosinophilic cytoplasm (Figure 2A, Box 1). A lymphoplasmacytic meningioma was suspected, and immunohistochemistry (IHC) was performed to confirm the diagnosis. The medium-sized lymphocytes mainly expressed CD20 (Figure 2B) and CD79a and were negative for CD5 (Figure 2C) and CD3; therefore, they could be assigned to the B-cell lineage, suggesting B-cell non-Hodgkin-lymphoma (B-NHL) accompanied by a physiological CD3, CD5 T-cell infiltrate. The B-lymphocytes and plasma cells also showed a monotypic expression of the immunoglobulin light chain kappa (kappa/lambda ratio: &gt;10/1, Figure 2D,E). Immunohistochemically, there was no evidence of aberrant expression of CD10, BCL6, CD23, CyclinD1, MUM1, EMA, or progesterone receptor and therefore, there was no evidence of B-CLL, mantle cell lymphoma, follicular lymphoma, or meningioma. The proliferation index (Ki-67) was low (~15%, Figure 2F), consistent with the diagnosis of indolent B-NHL.&lt;/p&gt;&lt;p&gt;Serum protein electrophoresis and immunofixation showed no serum immunoglobulin abnormalities. A sternal bone marrow biopsy was performed, with normal findings.&lt;/p&gt;&lt;p&gt;Primary intraventricular marginal zone B-cell lymphoma was diagnosed.&lt;/p&gt;&lt;p&gt;Extranodal marginal zone lymphoma (EMZL) is an indolent, small B-cell neoplasm that can be found in any extranodal location, but most frequently in the gastrointestinal tract (MALT lymphoma). [&lt;span&gt;1&lt;/span&gt;] In rare cases, MALT lymphomas may develop in tissues without mucosa, including the central nervous system. Ventricular invasion of a parenchymal primary CNS lymphoma occurs in up to 10.6% of cases, but an exclusively intraventricular form is very rare. [&lt;span&gt;1-3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;MALT lymphomas have the ability to mimic meningiomas on imaging, dural-based masses being the most common appearance. [&lt;span&gt;2&lt;/span&gt;] Despite the lack of mucosa in the brain tissue, it is suggested that intraventricular MALT lymphomas may be mistaken for meningiomas because arachnoid cap cells (contained within the choroid plexus) serve as a surrogate for mucosal epithel","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sterol imbalances and cholesterol-24-hydroxylase dysregulation is linked to the underlying progression of multiple sclerosis.","authors":"Lauren Griffiths, Kristen Hawkins, Eylan Yutuc, Roberto Angelini, Racheal Fosuah, Manuela Pacciarini, Alison Dickson, Neil Robertson, Laura Childs, Samantha Loveless, Emma Tallantyre, William J Griffiths, Yuqin Wang, Owain W Howell","doi":"10.1111/bpa.70001","DOIUrl":"https://doi.org/10.1111/bpa.70001","url":null,"abstract":"<p><p>Disability worsening in multiple sclerosis (MS) is linked to neurodegeneration. Cholesterol homeostasis is essential for normal brain function. CYP46A1, crucial for brain cholesterol turnover and reduced in some neurodegenerative diseases, is a potential neuroprotective target. We hypothesized that CYP46A1 is downregulated in MS brains and linked to cholesterol dysbalance. Mass spectrometric analysis of sterols was performed from matched plasma and cerebrospinal fluid (CSF) in an all-female MS cohort (n = 32, mean age = 33). Disability status was recorded at baseline and follow-up. MS brain tissue samples (n = 11; 7 females; ages 38-67; 10 Secondary Progressive MS, 1 Primary Progressive MS; Disease Duration: 13-49 years) and control samples (n = 8; 3 females; ages 41-68) analysed for pathological regions using mass spectrometry and RNA expression using in-situ hybridization. Significant dysregulation in 25-hydroxycholesterol, 27-hydroxycholesterol and 3β-hydroxycholestenoic acid in CSF correlated with disability at baseline and follow-up in the patient population. In brain tissue, reduced cholesterol, 24S-hydroxycholesterol and 24S,25-epoxycholesterol were observed in white matter lesions (p < 0.05), linked to CYP46A1 activity. CYP46A1 expression was enriched in neurons, with reductions in MS grey matter lesions and non-lesions compared to controls (p < 0.01). Cholesterol metabolism is dysregulated in MS and is associated with reduced neuron-specific CYP46A1 expression. Modulating CYP46A1, a druggable target, may benefit progressive MS.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70001"},"PeriodicalIF":5.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 6-year-old female with synchronous cerebellar and thalamic masses.","authors":"Wenjun Luo, Cuiyun Sun, Zhendong Jiang, Rongju Zhang, Wengao Zhang, Shizhu Yu","doi":"10.1111/bpa.70005","DOIUrl":"https://doi.org/10.1111/bpa.70005","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70005"},"PeriodicalIF":5.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 16-year-old female with an intrasellar mass","authors":"Yinbo Xiao,&nbsp;Can Yin,&nbsp;Junliang Lu,&nbsp;Shuangni Yu,&nbsp;Zhen Huo,&nbsp;Zhiyong Liang","doi":"10.1111/bpa.70002","DOIUrl":"10.1111/bpa.70002","url":null,"abstract":"&lt;p&gt;A 16-year-old girl presented to the clinic with a 2-year history of weight gain. In the last week, she had developed blepharoptosis and blurred vision, with headache and vomiting. She did not have a prior history of tumors. Physical examination showed a moon face, buffalo hump, and purpura. Laboratory findings showed elevated 24-hour urinary free cortisol (UFC) and plasma adrenocorticotropic hormone (ACTH). The low-dose dexamethasone suppression test failed to suppress cortisol production, but the high-dose test did. Magnetic resonance imaging (MRI) revealed a 15.9 × 10.1 × 12.8 mm&lt;sup&gt;3&lt;/sup&gt; sellar mass with heterogeneous T1 signal enhancement (Figure 1). It extended into the bilateral cavernous sinuses and the suprasellar cistern, impacting the optic chiasm. Surgery was pursued for a definitive diagnosis and tumor debulking (Box 1).&lt;/p&gt;&lt;p&gt;Histopathological examination revealed a biphasic tumor with a neuroendocrine and a mesenchymal component. The neuroendocrine component, with well-differentiated solid or glandular structures, showed positive staining for Synaptophysin (Syn), ACTH, and transcription factors T-PIT and INSM-1 but negative for PIT-1 and SF-1 (Figure 2). The mesenchymal component in the stromal background was composed of spindle or irregular cells with large nuclei and abundant eosinophilic cytoplasm. These tumor cells were positive for Desmin, MyoD1, and Myogenin (Figure 2). Unlike the neuroendocrine component, the mesenchymal component exhibited strong nuclear p53 positivity and loss of ATRX expression. Mitoses were frequent in the mesenchymal component (up to 8 per 10 HPF). The mitotic count was in keeping with the Ki67 labeling (the Ki67 index was significantly higher in the mesenchymal components [50%] compared with the epithelial cells [3%]). NGS testing identified several pathological mutations as follows: &lt;i&gt;DICER1&lt;/i&gt; (c.4860dup, p.Cys1621Leufs*31), &lt;i&gt;DICER1&lt;/i&gt; (c.5428G&gt;T, p.Asp1810Tyr), &lt;i&gt;TP53&lt;/i&gt; (c.740A&gt;T, p.N247I), &lt;i&gt;ATRX&lt;/i&gt; (c.594+1G&gt;T), and &lt;i&gt;PIK3CA&lt;/i&gt; copy-number gain.&lt;/p&gt;&lt;p&gt;Corticotrophin tumor/adenoma in association with primary intracranial sarcoma, DICER1-mutant.&lt;/p&gt;&lt;p&gt;This is a unique case of a young patient who presented with signs and symptoms of Cushing's disease and was diagnosed post-surgery as “corticotrophin tumor/adenoma associated with primary intracranial sarcoma, DICER1-mutant.” Primary intracranial sarcoma, DICER1-mutant (PIS-DICER1) is a rare molecularly defined entity. According to the 2021 World Health Organization (WHO) CNS tumor classification, it is defined as a primary intracranial sarcoma with distinctive morphology, typically showing immunophenotypic myogenic differentiation [&lt;span&gt;1&lt;/span&gt;]. DICER1 mutations are definite features, commonly along with TP53 mutations and ATRX inactivation. These tumors usually occur in young patients (median age at diagnosis as 6 years) and appear to be aggressive, notably at risk for DICER1 syndrome. Without appropriate genetic testing,","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of target-enriched enzymatic methylation sequencing for brain tumor classification from formalin-fixed paraffin embedded-derived DNA.","authors":"Quynh T Tran, Sujuan Jia, Md Zahangir Alom, Lu Wang, Charles G Mullighan, Ruth G Tatevossian, Brent A Orr","doi":"10.1111/bpa.70000","DOIUrl":"https://doi.org/10.1111/bpa.70000","url":null,"abstract":"<p><p>DNA methylation profiling by Illumina methylation array-based methods has revolutionized the molecular classification and diagnosis of brain tumors. A significant barrier to adopting these methods in a clinical environment is the requirement for specialized scanners, which results in high additional costs and a larger laboratory footprint. DNA sequencing-based alternatives are attractive because most clinical molecular pathology laboratories already use sequencers for other molecular assays. This study aimed to compare the utility of the newly developed sequencing-based enzymatic methyl sequencing (EM-seq) method paired with the Twist Human Methylome panel for brain tumor classification with standard Infinium Methylation BeadChip-based methods. We used DNA from fresh-frozen or formalin-fixed, paraffin-embedded (FFPE) brain cancer samples from 19 patients and 1 control sample to construct DNA libraries covering 3.98 million CpG sites. We developed and validated a bioinformatics pipeline to analyze target-enriched EM-seq (TEEM-seq) data in comparison with standard array-based methods for tumor classification and copy number profiling. We found high concordance between TEEM-seq and traditional methods, with high correlation coefficients (>0.98) between FFPE replicates. We successfully classified tumor samples into the expected molecular classes with robust prediction scores (>0.82). We observed that FFPE samples required a sequencing depth of at least 35x to achieve consistently high and reliable prediction scores. The TEEM-seq method has the potential to complement existing tumor classification methods and lower the barriers for the adoption of methylation profiling in routine clinical use.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70000"},"PeriodicalIF":5.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}