Interrogating malignant gliomas using released tumor DNA in cerebrospinal fluid

使用脑脊液中释放的肿瘤 DNA 检测恶性神经胶质瘤

• 批准号: 10610117
• 负责人: CHETAN BETTEGOWDA
• 金额: $ 36.71万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10610117
• 关键词: Alleles; Benchmarking; Biological Assay; Biological Markers; Biopsy; Blood; Body Fluids; Brain; Cancer Patient; Caring; Cerebrospinal Fluid; Clinical; DNA; Data; Detection; Development; Diagnosis; Diagnostic; Disease; Disease Progression; Dose; Evolution; Excision; Future; Genomics; Genotype; Glioma; Goals; Individual; Infection; Karnofsky Performance Status; Malignant Glioma; Malignant Neoplasms; Malignant neoplasm of brain; Measures; Molecular Evolution; Monitor; Multiple Sclerosis; Mutation; Necrosis; Neurosurgical Procedures; Normal tissue morphology; Operative Surgical Procedures; Outcome; Parents; Pathologic; Patients; Process; Prognosis; Radiation therapy; Recurrence; Recurrent tumor; Repeat Surgery; Research; Sampling; Somatic Mutation; Specific qualifier value; Specificity; Sputum; Steroids; Techniques; Testing; Time; Tissues; Tumor Burden; Tumor Tissue; Tumor-Derived; Uncertainty; Urine; Work; burden of illness; cancer biomarkers; cancer cell; cell free DNA; chemotherapy; cohort; diagnostic tool; digital; driver mutation; exome sequencing; experience; high risk; imaging modality; improved; insight; minimally invasive; mutant; neoplastic cell; neurosarcoidosis; novel therapeutics; optimal treatments; patient subsets; personalized therapeutic; radiological imaging; serial imaging; specific biomarkers; treatment effect; treatment response; tumor; tumor DNA; tumor progression

PROJECT SUMMARY There are no biomarkers that are currently used in the management of high-grade gliomas. Therefore, patients are often required to undergo invasive biopsies or surgical resection to differentiate disease progression from treatment related changes, quantify disease burden and track the molecular evolution of these difficult to treat cancers. In work performed to date, we have been able to demonstrate that CSF is a rich reservoir for tumor derived DNA. We are now expanding upon that work to develop a multi-analyte assay that will incorporate copy number changes, sub-chromosomal changes and somatic mutations. We anticipate that by looking at multiple analytes we will be able to improve sensitivity of the assay while also being able to have a more wholistic understanding of the cancer genotype. The specificity of this multi-analyte assay will be tested using CSF from individuals without cancer. In the short term, we anticipate that this approach will allow us to generate personalized biomarkers capable of tracking brain cancers and providing insights into the tumor genotype, thereby allowing clinicians to make more informed decisions in real-time. In the long term, we anticipate that we can gain a broader understanding of the CSF DNA composition in non-neoplastic states, such as multiple sclerosis, neurosarcoidosis or infection. This could have broad ranging impact on our ability to diagnose and monitor other disorders impacting the brain.

项目概要 目前没有生物标志物可用于治疗高级别神经胶质瘤。 因此，患者常常需要进行侵入性活检或手术切除 区分疾病进展和治疗相关变化，量化疾病负担和 追踪这些难以治疗的癌症的分子进化。在迄今为止所做的工作中，我们 已经能够证明脑脊液是肿瘤来源 DNA 的丰富库。我们现在 扩展该工作以开发包含拷贝数的多分析物测定 变化、亚染色体变化和体细胞突变。我们预计通过观察 多种分析物，我们将能够提高测定的灵敏度，同时还能够 对癌症基因型有更全面的了解。这种多分析物测定的特异性 将使用未患有癌症的个体的脑脊液进行测试。从短期来看，我们预计这 该方法将使我们能够生成能够追踪脑癌和 提供对肿瘤基因型的见解，从而使临床医生能够获得更多信息 实时决策。从长远来看，我们预计我们可以获得更广泛的了解 非肿瘤状态下的脑脊液 DNA 组成，例如多发性硬化症、神经结节病 或感染。这可能会对我们诊断和监测其他疾病的能力产生广泛的影响 影响大脑的疾病。

项目成果

Detection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis using aneuploidy and mutation identification in plasma.

使用血浆中的非整倍性和突变鉴定检测神经纤维瘤病患者的恶性周围神经鞘肿瘤。

• 发表时间: 2022-03-04
• 影响因子: 7.7
• 作者: Mattox, Austin K;Douville, Christopher;Silliman, Natalie;Ptak, Janine;Dobbyn, Lisa;Schaefer, Joy;Popoli, Maria;Blair, Cherie;Judge, Kathy;Pollard, Kai;Pratilas, Christine;Blakeley, Jaishri;Rodriguez, Fausto;Papadopoulos, Nickolas;Belzberg, A
• 通讯作者: Belzberg, A

Genotype-Phenotype Correlations in Neurofibromatosis and Their Potential Clinical Use.

神经纤维瘤病的基因型-表型相关性及其潜在的临床用途。

• 发表时间: 2021
• 影响因子: 9.9
• 作者: Bettegowda, Chetan;Upadhayaya, Meena;Evans, D Gareth;Kim, AeRang;Mathios, Dimitrios;Hanemann, Clemens O;REiNS International Collaboration
• 通讯作者: REiNS International Collaboration

Genomic Landscape of Intramedullary Spinal Cord Gliomas.

髓内脊髓胶质瘤的基因组景观。

• 发表时间: 2019
• 影响因子: 4.6
• 作者: Zhang, Ming;Iyer, Rajiv R;Azad, Tej D;Wang, Qing;Garzon;Wang, Joanna;Liu, Ann;Burger, Peter;Eberhart, Charles;Rodriguez, Fausto J;Sciubba, Daniel M;Wolinsky, Jean;Gokaslan, Ziya;Groves, Mari L;Jallo, George I;Bettegowda, C
• 通讯作者: Bettegowda, C

Liquid biopsy for pediatric diffuse midline glioma: a review of circulating tumor DNA and cerebrospinal fluid tumor DNA.

儿童弥漫性中线胶质瘤的液体活检：循环肿瘤 DNA 和脑脊液肿瘤 DNA 的回顾。

• 发表时间: 2020-01-01
• 影响因子: 4.1
• 作者: Azad, Tej D;Jin, Michael C;Bernhardt, Lydia J;Bettegowda, Chetan
• 通讯作者: Bettegowda, Chetan

Pembrolizumab for patients with leptomeningeal metastasis from solid tumors: efficacy, safety, and cerebrospinal fluid biomarkers.

帕博利珠单抗治疗实体瘤软脑膜转移患者：疗效、安全性和脑脊液生物标志物。

• 发表时间: 2021
• 作者: Naidoo, Jarushka;Schreck, Karisa C;Fu, Wei;Hu, Chen;Carvajal;Connolly, Roisin M;Santa;Lipson, Evan J;Holdhoff, Matthias;Forde, Patrick M;Douville, Christopher;Riemer, Joanne;Barnes, Amanda;Redmond, Kristin J
• 通讯作者: Redmond, Kristin J