60 results on '"Adam Resnick"'
Search Results
2. Evaluating preclinical evidence for clinical translation in childhood brain tumours: Guidelines from the CONNECT, PNOC, and ITCC brain networks
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Chris Jones, Karin Straathof, Maryam Fouladi, Darren Hargrave, Michael Prados, Adam Resnick, Francois Doz, David T.W. Jones, and Sabine Mueller
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pediatric ,CNS ,preclinical ,models ,translational ,in vitro ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Clinical outcomes for many childhood brain tumours remain poor, despite our increasing understanding of the underlying disease biology. Advances in molecular diagnostics have refined our ability to classify tumour types and subtypes, and efforts are underway across multiple international paediatric neuro-oncology consortia to take novel biological insights in the worst prognosis entities into innovative clinical trials. Whilst for the first time we are designing such studies on the basis of disease-specific biological data, the levels of preclincial evidence in appropriate model systems on which these trials are initiated is still widely variable. We have considered these issues between CONNECT, PNOC and ITCC-Brain, and developed a framework in which we can assess novel concepts being brought forward for possible clinical translation. Whilst not intended to be proscriptive for every possible circumstance, these criteria provide a basis for self-assessment of evidence by laboratory scientists, and a platform for discussion and rational decision-making prior to moving forward clinically.
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- 2023
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3. Indigenous peoples and inclusion in clinical and genomic research: Understanding the history and navigating contemporary engagement
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Angela Waanders, Alex Brown, Nadine R. Caron, Alexa Plisiewicz, Sean T. McHugh, Thinh Q. Nguyen, Kaitlin Lehmann, Jeffrey Stevens, Phillip J. Storm, Adam Resnick, Tom Belle Davidson, Sabine Mueller, and Cassie Kline
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Diversity ,Equity ,Inclusion ,Indigenous people ,Clinical research ,Pediatric neuro-oncology ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Despite significant improvements in pediatric cancer survival outcomes, there remain glaring disparities in under-represented racial and ethnic groups that warrant mitigation by the scientific and clinical community. To address and work towards eliminating such disparities, the Pacific Pediatric Neuro-Oncology Consortium (PNOC) and Children's Brain Tumor Network (CBTN) established a Diversity, Equity, and Inclusion (DEI) working group in 2020. The DEI working group is dedicated to improving access to care for all pediatric patients with central nervous system (CNS) tumors, broadening diversity within the research community, and providing sustainable data-driven solutions. To this end, the DEI working group aims to coordinate regular educational sessions centered on critical DEI topics in pediatric research and clinical care of pediatric patients, with a focus on pediatric neuro-oncology. In April 2022, the group led a moderated panel of experts on Indigenous Peoples’ rights and participation in clinical research activities. The following paper serves to provide the scientific community a perspective on how to prioritize the inclusion of Indigenous Peoples in research with cultural sensitivity and with the intent of improving not only representation, but patient outcomes regardless of patient race, ethnicity, or socioeconomic background.
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- 2023
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4. Retrospective dataset and survey analyses identify gaps in data collection for craniopharyngioma and priorities of patients and families affected by the disease
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Emily Marshall, Nikhil Joshi, Julia Crowley, Shana McCormack, Sylvia Cheng, Walter Faig, Phillip B. Storm, Adam Resnick, Sabine Mueller, Fatema Malbari, and Cassie Kline
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Craniopharyngioma ,Quality of life ,Molecular sequencing ,Neuroendocrine ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: Craniopharyngioma is a rare, low-grade tumor located in the suprasellar region of the brain, near critical structures like the pituitary gland. Here, we concurrently investigate the status of clinical and genomic data in a retrospective craniopharyngioma cohort and survey-based data to better understand patient-relevant outcomes associated with existing therapies and provide a foundation to inform new treatment strategies. Methods: Clinical, genomic, and outcome data for a retrospective cohort of patients with craniopharyngioma were collected and reviewed through the Children's Brain Tumor Network (CBTN) database. An anonymous survey was distributed to patients and families with a diagnosis of craniopharyngioma to understand their experiences throughout diagnosis and treatment. Results: The CBTN repository revealed a large proportion of patients (40 – 70%) with specimens that are available for sequencing but lacked relevant quality of life (QoL) and functional outcomes. Frequencies of reported patient comorbidities ranged from 20–35%, which is significantly lower than historically reported. Survey results from 159 patients/families identified differences in treatment considerations at time of diagnosis versus time of recurrence. In retrospective review, patients and families identified preference for therapy that would improve QoL, rather than decrease risk of recurrence (mean 3.9 vs. 4.4 of 5) and identified endocrine issues as having the greatest impact on patients’ lives. Conclusions: This work highlights the importance of prospective collection of QoL and functional metrics alongside robust clinical and molecular correlates in individuals with craniopharyngioma. Such comprehensive measures will facilitate biologically relevant therapeutic strategies that also prioritize patient needs.
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- 2023
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5. Unsupervised machine learning using K-means identifies radiomic subgroups of pediatric low-grade gliomas that correlate with key molecular markers
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Debanjan Haldar, Anahita Fathi Kazerooni, Sherjeel Arif, Ariana Familiar, Rachel Madhogarhia, Nastaran Khalili, Sina Bagheri, Hannah Anderson, Ibraheem Salman Shaikh, Aria Mahtabfar, Meen Chul Kim, Wenxin Tu, Jefferey Ware, Arastoo Vossough, Christos Davatzikos, Phillip B. Storm, Adam Resnick, and Ali Nabavizadeh
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Radiomics ,Radiogenomics ,Pediatric low-grade glioma ,Unsupervised machine learning ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: Despite advancements in molecular and histopathologic characterization of pediatric low-grade gliomas (pLGGs), there remains significant phenotypic heterogeneity among tumors with similar categorizations. We hypothesized that an unsupervised machine learning approach based on radiomic features may reveal distinct pLGG imaging subtypes. Methods: Multi-parametric MR images (T1 pre- and post-contrast, T2, and T2 FLAIR) from 157 patients with pLGGs were collected and 881 quantitative radiomic features were extracted from tumorous region. Clustering was performed using K-means after applying principal component analysis (PCA) for feature dimensionality reduction. Molecular and demographic data was obtained from the PedCBioportal and compared between imaging subtypes. Results: K-means identified three distinct imaging-based subtypes. Subtypes differed in mutational frequencies of BRAF (p < 0.05) as well as the gene expression of BRAF (p
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- 2023
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6. Genomic Findings in Bone Blood Paired DNA Comparison of Nonsyndromic Craniosynostosis
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Yiran Guo, , PhD, Christopher L. Kalmar, MD, MBA, Xiaoyan Huang, MS, Bo Zhang, BS, Yuankun Zhu, BS, Stephanie Stefankiewicz, BS, Mateusz Koptyra, PhD, Jennifer Mason, BA, Tatiana Patton, MS, Elizabeth Appert, MS, Lina Lopez, BA, Catherine Sullivan, BS, Anna R. Carlson, MD, Mychajlo S. Kosyk, BA, Zachary D. Zapatero, BS, Philip B. Storm, MD, Jordan W. Swanson, MD, MSc, Scott P. Bartlett, MD, Joseph M. Serletti, MD, Adam Resnick, PhD, and Jesse A. Taylor, MD
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Surgery ,RD1-811 - Published
- 2021
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7. Natural Language Processing (NLP) in Qualitative Public Health Research: A Proof of Concept Study
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William Leeson, Adam Resnick, Daniel Alexander, and John Rovers
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Social sciences (General) ,H1-99 - Abstract
Qualitative data-analysis methods provide thick, rich descriptions of subjects’ thoughts, feelings, and lived experiences but may be time-consuming, labor-intensive, or prone to bias. Natural language processing (NLP) is a machine learning technique from computer science that uses algorithms to analyze textual data. NLP allows processing of large amounts of data almost instantaneously. As researchers become conversant with NLP, it is becoming more frequently employed outside of computer science and shows promise as a tool to analyze qualitative data in public health. This is a proof of concept paper to evaluate the potential of NLP to analyze qualitative data. Specifically, we ask if NLP can support conventional qualitative analysis, and if so, what its role is. We compared a qualitative method of open coding with two forms of NLP, Topic Modeling, and Word2Vec to analyze transcripts from interviews conducted in rural Belize querying men about their health needs. All three methods returned a series of terms that captured ideas and concepts in subjects’ responses to interview questions. Open coding returned 5–10 words or short phrases for each question. Topic Modeling returned a series of word-probability pairs that quantified how well a word captured the topic of a response. Word2Vec returned a list of words for each interview question ordered by which words were predicted to best capture the meaning of the passage. For most interview questions, all three methods returned conceptually similar results. NLP may be a useful adjunct to qualitative analysis. NLP may be performed after data have undergone open coding as a check on the accuracy of the codes. Alternatively, researchers can perform NLP prior to open coding and use the results to guide their creation of their codebook.
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- 2019
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8. We Built it, But Did They Come: Veterans’ Use of VA Healthcare System-Provided Complementary and Integrative Health Approaches
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Stephanie L. Taylor, Hannah M. Gelman, Rian DeFaccio, Jamie Douglas, Matthew J. Hawrilenko, Nathan K. McGinty, Adam Resnick, Nathan C. Tomlanovich, Joy Toyama, Alison M. Whitehead, Benjamin Kligler, and Steven B. Zeliadt
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Complementary Therapies ,Male ,meditation ,Clinical Sciences ,Veterans Health ,veteran ,Musculoskeletal Pain ,Clinical Research ,Integrated ,General & Internal Medicine ,Complementary and Integrative Health ,Behavioral and Social Science ,Internal Medicine ,Humans ,Retrospective Studies ,Veterans ,Pain Research ,Health Services ,Post-Traumatic Stress Disorder (PTSD) ,Anxiety Disorders ,United States ,United States Department of Veterans Affairs ,Mental Health ,Good Health and Well Being ,yoga ,Musculoskeletal ,Female ,Chronic Pain ,Delivery of Health Care ,Mind and Body ,complementary and alternative medicine - Abstract
Background Interest in complementary and integrative health (CIH) approaches, such as meditation, yoga, and acupuncture, continues to grow. The evidence of effectiveness for some CIH approaches has increased in the last decade, especially for pain, with many being recommended in varying degrees in national guidelines. To offer nonpharmacological health management options and meet patient demand, the nation’s largest integrated healthcare system, the Veterans Health Administration (VA), greatly expanded their provision of CIH approaches recently. Objective This paper addressed the questions of how many VA patients might use CIH approaches and chiropractic care if they were available at modest to no fee, and would patients with some health conditions or characteristics be more likely than others to use these therapies. Design Using electronic medical records, we conducted a national, three-year, retrospective analysis of VA patients’ use of eleven VA-covered therapies: chiropractic care, acupuncture, Battlefield Acupuncture, biofeedback, clinical hypnosis, guided imagery, massage therapy, meditation, Tai Chi/Qigong, and yoga. Participants We created a national cohort of veterans using VA healthcare from October 2016–September 2019. Key Results Veterans’ use of these approaches increased 70% in three years. By 2019, use was 5.7% among all VA patients, but highest among patients with chronic musculoskeletal pain (13.9%), post-traumatic stress disorder (PTSD; 10.6%), depression (10.4%), anxiety (10.2%), or obesity (7.8%). The approach used varied by age and race/ethnicity, with women being uniformly more likely than men to use each approach. Patients having chronic musculoskeletal pain, obesity, anxiety, depression, or PTSD were more likely than others to use each of the approaches. Conclusions Veterans’ use of some approaches rapidly grew recently and was robust, especially among patients most in need. This information might help shape federal/state health policy on the provision of evidence-based CIH approaches and guide other healthcare institutions considering providing them.
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- 2022
9. Molecular and clinicopathologic characteristics of gliomas with EP300::BCOR fusions
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Zhichao Wu, Sharika Rajan, Hye-Jung Chung, Mark Raffeld, Pavalan Panneer Selvam, Leonille Schweizer, Arie Perry, David Samuel, Caterina Giannini, Aditya Ragunathan, Matthew P. Frosch, Michael S. Marshall, Daniel R. Boué, Kliment Donev, Stewart G. Neill, Igor Fernandes, Adam Resnick, Brian Rood, Thomas J. Cummings, Anne F. Buckley, Linda Szymanski, Osorio Lopes Abath Neto, Leor Zach, Howard Colman, Samuel Cheshier, Jennifer Ziskin, Manoj Tyagi, David Capper, Zied Abdullaev, Patrick J. Cimino, Martha Quezado, Drew Pratt, and Kenneth Aldape
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Repressor Proteins ,Cellular and Molecular Neuroscience ,Proto-Oncogene Proteins ,Humans ,Glioma ,Neurology (clinical) ,E1A-Associated p300 Protein ,Pathology and Forensic Medicine - Published
- 2022
10. Data from Upfront Biology-Guided Therapy in Diffuse Intrinsic Pontine Glioma: Therapeutic, Molecular, and Biomarker Outcomes from PNOC003
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Sabine Mueller, Javad Nazarian, Sebastian M. Waszak, Adam Resnick, Michael Prados, Annette Molinaro, Michael Berens, Sara Byron, Winnie Liang, John Kuhn, Adam Kraya, Jo Lynne Rokita, Krutika S. Gaonkar, Bo Zhang, Sridevi Yadavilli, Jie Zhang, Madhuri Kambhampati, Yalan Zhang, Tracy Luks, Javier Villanueva-Meyer, Roger J. Packer, Anu Banerjee, John R. Crawford, Nalin Gupta, Erin R. Bonner, Lindsay Kilburn, Payal Jain, and Cassie Kline
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Purpose:PNOC003 is a multicenter precision medicine trial for children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG).Patients and Methods:Patients (3–25 years) were enrolled on the basis of imaging consistent with DIPG. Biopsy tissue was collected for whole-exome and mRNA sequencing. After radiotherapy (RT), patients were assigned up to four FDA-approved drugs based on molecular tumor board recommendations. H3K27M-mutant circulating tumor DNA (ctDNA) was longitudinally measured. Tumor tissue and matched primary cell lines were characterized using whole-genome sequencing and DNA methylation profiling. When applicable, results were verified in an independent cohort from the Children's Brain Tumor Network (CBTN).Results:Of 38 patients enrolled, 28 patients (median 6 years, 10 females) were reviewed by the molecular tumor board. Of those, 19 followed treatment recommendations. Median overall survival (OS) was 13.1 months [95% confidence interval (CI), 11.2–18.4] with no difference between patients who followed recommendations and those who did not. H3K27M-mutant ctDNA was detected at baseline in 60% of cases tested and associated with response to RT and survival. Eleven cell lines were established, showing 100% fidelity of key somatic driver gene alterations in the primary tumor. In H3K27-altered DIPGs, TP53 mutations were associated with worse OS (TP53mut 11.1 mo; 95% CI, 8.7–14; TP53wt 13.3 mo; 95% CI, 11.8–NA; P = 3.4e−2), genome instability (P = 3.1e−3), and RT resistance (P = 6.4e−4). The CBTN cohort confirmed an association between TP53 mutation status, genome instability, and clinical outcome.Conclusions:Upfront treatment-naïve biopsy provides insight into clinically relevant molecular alterations and prognostic biomarkers for H3K27-altered DIPGs.
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- 2023
11. Supplementary Figure from Upfront Biology-Guided Therapy in Diffuse Intrinsic Pontine Glioma: Therapeutic, Molecular, and Biomarker Outcomes from PNOC003
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Sabine Mueller, Javad Nazarian, Sebastian M. Waszak, Adam Resnick, Michael Prados, Annette Molinaro, Michael Berens, Sara Byron, Winnie Liang, John Kuhn, Adam Kraya, Jo Lynne Rokita, Krutika S. Gaonkar, Bo Zhang, Sridevi Yadavilli, Jie Zhang, Madhuri Kambhampati, Yalan Zhang, Tracy Luks, Javier Villanueva-Meyer, Roger J. Packer, Anu Banerjee, John R. Crawford, Nalin Gupta, Erin R. Bonner, Lindsay Kilburn, Payal Jain, and Cassie Kline
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Supplementary Figure from Upfront Biology-Guided Therapy in Diffuse Intrinsic Pontine Glioma: Therapeutic, Molecular, and Biomarker Outcomes from PNOC003
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- 2023
12. Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses
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David Raleigh, William Chen, Abrar Choudhury, Mark Youngblood, Mei-Yin Polley, Calixto-Hope Lucas, Kanish Mirchia, Sybren Maas, Abigail Suwala, Minhee Won, James Bayley, Akdes Harmanci, Arif Harmanci, Tiemo Klisch, Minh Nguyen, Harish Vasudevan, Kathleen McCortney, Theresa Yu, Varun Bhave, Tai-Chung Lam, Jenny Pu, Gilberto Leung, Jason Chang, Haley Perlow, Joshua Palmer, Christine Haberler, Anna Berghoff, Matthias Preusser, Theodore Nicolaides, Christian Mawrin, Sameer Agnihotri, Adam Resnick, Brian Rood, Jessica Chew, Jacob Young, Lauren Boreta, Steve Braunstein, Jessica Schulte, Nicholas Butowski, Sandro Santagata, David Spetzler, Nancy Ann Oberheim Bush, Javier Villanueva-Meyer, James Chandler, David Solomon, C Rogers, Stephanie Pugh, Minesh Mehta, Penny Sneed, Mitchel Berger, Craig Horbinski, Michael McDermott, Arie Perry, Wenya Bi, Akash Patel, Felix Sahm, and Stephen Magill
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Background Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and current indications for postoperative radiotherapy are controversial. Recent studies have proposed prognostic meningioma classification systems using DNA methylation profiling, copy number variants, DNA sequencing, RNA sequencing, histology, or integrated models based on multiple combined features. Targeted gene expression profiling has generated robust biomarkers integrating multiple molecular features for other cancers, but is understudied for meningiomas. Methods Targeted gene expression profiling was performed on 173 meningiomas and an optimized gene expression biomarker (34 genes) and risk score (0 to 1) was developed to predict clinical outcomes. Clinical and analytical validation was performed on independent meningiomas from 12 institutions across 3 continents (N = 1856), including 103 meningiomas from a prospective clinical trial. Gene expression biomarker performance was compared to 9 other classification systems. Results The gene expression biomarker improved discrimination of postoperative meningioma outcomes compared to all other classification systems tested in the independent clinical validation cohort for local recurrence (5-year area under the curve [AUC] 0.81) and overall survival (5-year AUC 0.80). The increase in area under the curve compared to the current standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval [CI] 0.07–0.17, P
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- 2023
13. Changes in Use of Complementary and Integrative Health Therapies at the Veterans Affairs: Findings from a Whole Health System Pilot Program
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Adam Resnick, Steven B. Zeliadt, David A. Ganz, Corrina Moucheraud, Emmeline Chuang, Elizabeth M. Yano, and Stephanie L. Taylor
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- 2023
14. Radiomics and radiogenomics in pediatric neuro-oncology: A review
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Rachel Madhogarhia, Debanjan Haldar, Sina Bagheri, Ariana Familiar, Hannah Anderson, Sherjeel Arif, Arastoo Vossough, Phillip Storm, Adam Resnick, Christos Davatzikos, Anahita Fathi Kazerooni, and Ali Nabavizadeh
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General Medicine - Abstract
The current era of advanced computing has allowed for the development and implementation of the field of radiomics. In pediatric neuro-oncology, radiomics has been applied in determination of tumor histology, identification of disseminated disease, prognostication, and molecular classification of tumors (ie, radiogenomics). The field also comes with many challenges, such as limitations in study sample sizes, class imbalance, generalizability of the methods, and data harmonization across imaging centers. The aim of this review paper is twofold: first, to summarize existing literature in radiomics of pediatric neuro-oncology; second, to distill the themes and challenges of the field and discuss future directions in both a clinical and technical context.
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- 2022
15. Abstract 3565: Establishing a multimodal data warehousing platform to accelerate discoveries in pediatric brain tumors for the Children’s Brain Tumor Network
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Bailey K. Farrow, Nicholas Van Kuren, Nathan Young, Christopher Friedman, Meen Chul Kim, Alex Lubneuski, Jennifer Mason, Thinh (Bin) Nguyen, Zeinab Helili, Elizabeth Frenkel, Catherine Sullivan, Ariana Familiar, Yuankun Zhu, Mateusz Koptyra, Tatiana Patton, Jena Lilly, Phillip B. Storm, Adam Resnick, and Allison P. Heath
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Cancer Research ,Oncology - Abstract
Brain tumors are the leading cause of disease-related death in children and young adults ages 0-19 in largely populated countries such as the United States. In one year alone, 4,000 children and young adults will be diagnosed with a brain or central nervous system tumor in the United States. Brain tumors are complex and difficult to treat in growing children, with current treatments oftentimes causing significant and lifelong side effects. Furthermore, there have only been five drugs in the last 20 years approved by the FDA to treat pediatric brain tumors. Founded in 2011, the Children’s Brain Tumor Network (CBTN) is focused on accelerating the pace of translational research, the discovery of new treatments, and informing precision medicine for children diagnosed with brain tumors. CBTN comprises 32 member institutions/hospitals having over 4700 patient subjects enrolled, spanning 30+ brain tumor diagnoses, over 66,000 biobanked samples and 150 preclinical models. Longitudinal clinical data is also collected for every subject that is enrolled in the observational protocol. Through large scale data generation efforts funded by the NCI and foundational support, CBTN has whole genome, RNA-seq and other molecular characterization for over half of the enrolled patient population. Additionally, efforts have been underway to collect all pathology and radiology imaging and reporting for the subjects. With sequencing being done by multiple vendors, imaging protocols being different across multiple hospitals, and complex clinical treatment and longitudinal follow up data being translated from EHR systems, CBTN has created a rich, but complex, data landscape that is the largest of its kind in the world. In order to accelerate the process of going from data to cures, the data needs to be centralized, organized, and easily distributable. To do this, CBTN has built a first of its kind data workflow that acts as the inventory system for its various data assets. Using a modern data stack including dbt, PostgresSQL, Meltano and AWS, combined with utilization of FHIR as an interchange standard, data from multiple disparate sources such as REDcap, EHR systems, and PAC systems flow in near “real-time” to be utilized as integrated data resources The result of this modern, multimodal, and multi-institutional warehouse allows CBTN to distribute data quickly and accurately to translational researchers around the world and contribute data to key research efforts such as AACR Project Genie, Kids First Data Resource Center, NCI Childhood Cancer Data Initiative, and the NCI’s Open Targets Platform. Citation Format: Bailey K. Farrow, Nicholas Van Kuren, Nathan Young, Christopher Friedman, Meen Chul Kim, Alex Lubneuski, Jennifer Mason, Thinh (Bin) Nguyen, Zeinab Helili, Elizabeth Frenkel, Catherine Sullivan, Ariana Familiar, Yuankun Zhu, Mateusz Koptyra, Tatiana Patton, Jena Lilly, Phillip B. Storm, Adam Resnick, Allison P. Heath. Establishing a multimodal data warehousing platform to accelerate discoveries in pediatric brain tumors for the Children’s Brain Tumor Network. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3565.
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- 2023
16. Abstract 4256: cBioPortal for Cancer Genomics
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Ino de Bruijn, Tali Mazor, Adam Abeshouse, Diana Baiceanu, Stephanie Carrero, Elena Garcia Lara, Benjamin Gross, David M. Higgins, Prasanna K. Jagannathan, Priti Kumari, Ritika Kundra, Bryan Lai, Xiang Li, James Lindsay, Aaron Lisman, Divya Madala, Ramyasree Madupuri, Angelica Ochoa, Yusuf Ziya Özgül, Oleguer Plantalech, Sander Rodenburg, Baby Anusha Satravada, Robert Sheridan, Lucas Sikina, Jessica Singh, S Onur Sumer, Yichao Sun, Pim van Nierop, Avery Wang, Manda Wilson, Hongxin Zhang, Gaofei Zhao, Sjoerd van Hagen, Ugur Dogrusoz, Allison Heath, Adam Resnick, Trevor J. Pugh, Chris Sander, Ethan Cerami, Jianjiong Gao, and Nikolaus Schultz
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Cancer Research ,Oncology - Abstract
cBioPortal for Cancer Genomics is an open-source platform for interactive, exploratory analysis of large-scale clinico-genomic data sets. cBioPortal provides a suite of user-friendly visualizations and analyses, including OncoPrints, mutation “lollipop” plots, variant interpretation, group comparison, survival analysis, expression correlation analysis, alteration enrichment analysis, cohort and patient-level visualization. The public site (https://www.cbioportal.org) is accessed by >35,000 unique visitors each month and hosts data from >350 studies spanning individual labs and large consortia. In addition, at least 74 instances of cBioPortal are installed at academic institutions and companies worldwide. To better support all users, we unified our documentation (https://docs.cbioportal.org) and added a user guide and an ongoing series of ‘how-to’ videos to address common questions. In 2022 we added 32 studies (>38,000 samples) to the public site. In addition, we added a nonsynonymous tumor mutation burden (TMB) value for all samples and enhanced the TCGA PanCancer Atlas studies with DNA methylation and treatment data. All data is available in the cBioPortal Datahub: https://github.com/cBioPortal/datahub. We also host a dedicated instance for AACR Project GENIE, enabling access to the GENIE cohort of >165,000 clinically sequenced samples from 19 institutions (https://genie.cbioportal.org). The GENIE Biopharma Collaborative (BPC) enables the collection of comprehensive clinical annotations, including response, outcome, and treatment history. The first BPC cohorts are now available: ~2,000 non-small cell lung cancer samples and ~1,500 colorectal cancer samples. Support for multimodal data analysis has been a major focus, including several new integrations with external tools. Single cell data is now available in the CPTAC GBM study and can be visualized throughout cBioPortal, and via integration with cellxgene. On the patient page, H&E and mIF images can be visualized via integration with Minerva, and the genomic overview now integrates IGV. We continue to enhance existing features. In the study view, users can now add charts comparing categorical vs continuous data, and the plots tab includes a heatmap option. We replaced the existing fusion data type with a generalized structural variant data type that supports detailed information including breakpoints and orientation, to enable new visualizations and analyses. Pathway level analysis has been extended with a new integration with NDEx. cBioPortal is fully open source (https://github.com/cBioPortal/). Development is a collaborative effort among groups at Memorial Sloan Kettering Cancer Center, Dana-Farber Cancer Institute, Children’s Hospital of Philadelphia, Princess Margaret Cancer Centre, Caris Life Sciences, Bilkent University and The Hyve. We welcome open source contributions from others in the cancer research community. Citation Format: Ino de Bruijn, Tali Mazor, Adam Abeshouse, Diana Baiceanu, Stephanie Carrero, Elena Garcia Lara, Benjamin Gross, David M. Higgins, Prasanna K. Jagannathan, Priti Kumari, Ritika Kundra, Bryan Lai, Xiang Li, James Lindsay, Aaron Lisman, Divya Madala, Ramyasree Madupuri, Angelica Ochoa, Yusuf Ziya Özgül, Oleguer Plantalech, Sander Rodenburg, Baby Anusha Satravada, Robert Sheridan, Lucas Sikina, Jessica Singh, S Onur Sumer, Yichao Sun, Pim van Nierop, Avery Wang, Manda Wilson, Hongxin Zhang, Gaofei Zhao, Sjoerd van Hagen, Ugur Dogrusoz, Allison Heath, Adam Resnick, Trevor J. Pugh, Chris Sander, Ethan Cerami, Jianjiong Gao, Nikolaus Schultz. cBioPortal for Cancer Genomics. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4256.
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- 2023
17. Generation and multi-dimensional profiling of a childhood cancer cell line atlas defines new therapeutic opportunities
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Claire Xin Sun, Paul Daniel, Gabrielle Bradshaw, Hui Shi, Melissa Loi, Nicole Chew, Sarah Parackal, Vanessa Tsui, Yuqing Liang, Mateusz Koptyra, Shazia Adjumain, Christie Sun, Wai Chin Chong, Dasun Fernando, Caroline Drinkwater, Motahhareh Tourchi, Dilru Habarakada, Dhanya Sooraj, Diana Carvalho, Phillip B. Storm, Valerie Baubet, Leanne C. Sayles, Elisabet Fernandez, Thy Nguyen, Mia Pörksen, Anh Doan, Duncan E. Crombie, Monty Panday, Nataliya Zhukova, Matthew D. Dun, Louise E. Ludlow, Bryan Day, Brett W. Stringer, Naama Neeman, Jeffrey A. Rubens, Eric H. Raabe, Maria Vinci, Vanessa Tyrrell, Jamie I. Fletcher, Paul G. Ekert, Biljana Dumevska, David S. Ziegler, Maria Tsoli, Nur Farhana Syed Sulaiman, Amos Hong Pheng Loh, Sharon Yin Yee Low, E. Alejandro Sweet-Cordero, Michelle Monje, Adam Resnick, Chris Jones, Peter Downie, Bryan Williams, Joseph Rosenbluh, Daniel Gough, Jason E. Cain, and Ron Firestein
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Cancer Research ,Oncology - Published
- 2023
18. Discovery and functional characterization of the oncogenicity and targetability of a novel
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Payal, Jain, Sudarshan, Iyer, Joshua, Straka, Lea F, Surrey, Jennifer, Pogoriler, Harry, Han, Tiffany, Smith, Christine, Busch, Elizabeth, Fox, Marilyn, Li, Angela J, Waanders, Adam, Resnick, and Monika A, Davare
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Mice ,Proto-Oncogene Proteins ,Hemangiosarcoma ,NIH 3T3 Cells ,Humans ,Animals ,Protein-Tyrosine Kinases ,Gene Fusion ,Receptor, Notch1 ,Child ,Protein Kinase Inhibitors - Abstract
Angiosarcomas are rare, malignant soft tissue tumors in children that arise in a wide range of anatomical locations and have limited targeted therapies available. Here, we report a rare case of a pediatric angiosarcoma (pAS) with Li-Fraumeni syndrome (LFS) expressing a novel
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- 2022
19. Automated segmentation of pediatric brain tumors based on multi-parametric MRI and deep learning
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Rachel Madhogarhia, Anahita Fathi Kazerooni, Sherjeel Arif, Jeffrey B. Ware, Ariana M. Familiar, Lorenna Vidal, Sina Bagheri, Hannah Anderson, Debanjan Haldar, Sophie Yagoda, Erin Graves, Michael Spadola, Rachel Yan, Nadia Dahmane, Chiharu Sako, Arastoo Vossough, Phillip Storm, Adam Resnick, Christos Davatzikos, and Ali Nabavizadeh
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- 2022
20. MODL-28. Patient-derived, three-dimensional organoid platform for pediatric brain tumor modeling
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Baubet, Valerie, primary, Beale, David, additional, Mariarita, Santi, additional, Viaene, Angela, additional, Madsen, Peter, additional, Jacob, Fadi, additional, Ming, Guo-li, additional, Hongjun, Song, additional, Phillip, Storm, additional, Koptyra, Mateusz, additional, and Adam, Resnick, additional
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- 2022
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21. Hijacking a neurodevelopmental epigenomic program in metastatic dissemination of medulloblastoma
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Han Zou, Bradley Poore, Emily Brown, Jieqi Qian, Bin Xie, Evridiki Asimakidou, Vladislav Razskazovskiy, Deanna Ayrapetian, Vaibhav Sharma, Shunjin Xia, Fei Liu, Apeng Chen, Yongchang Guan, Zhengwei Li, Siyi Wanggou, Olivier Saulnier, Michelle Ly, Wendy Fellows-Mayle, Guifa Xi, Tadanori Tomita, Adam Resnick, Stephen Mack, Eric Raabe, Charles Eberhart, Dandan Sun, Beth Stronach, Sameer Agnihotri, Gary Kohanbash, Songjian Lu, Karl Herrup, Jeremy Rich, George K. Gittes, Alberto Broniscer, Zhongliang Hu, Xuejun Li, Ian Pollack, Robert Friedlander, Sarah Hainer, Michael Taylor, and Baoli Hu
- Abstract
How dysregulation of neurodevelopment relates to medulloblastoma (MB), the most common pediatric brain tumor, remains elusive. Here, we uncovered a neurodevelopmental epigenomic program being hijacked to induce MB metastatic dissemination. Unsupervised analyses by integrating publicly available datasets with our newly generated data revealed that SMARCD3/BAF60C regulates DAB1-mediated Reelin signaling in Purkinje cell migration and MB metastasis by orchestrating cis-regulatory elements (CREs) at the DAB1 locus. We further identified that a core set of transcription factors, enhancer of zeste homolog 2 (EZH2) and nuclear factor I X (NFIX), coordinates with the CREs at the SMARCD3 locus to form a chromatin hub for controlling SMARCD3 expression in the developing cerebellum and metastatic MB. Elevated SMARCD3 activates Reelin/DAB1-mediated Src kinase signaling, resulting in MB response to Src inhibition. These data deepen our understanding of how neurodevelopmental programming influences disease progression and provide a potential therapeutic option for MB patients.
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- 2022
22. Upfront Biology-Guided Therapy in Diffuse Intrinsic Pontine Glioma: Therapeutic, Molecular, and Biomarker Outcomes from PNOC003
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Cassie Kline, Payal Jain, Lindsay Kilburn, Erin R. Bonner, Nalin Gupta, John R. Crawford, Anu Banerjee, Roger J. Packer, Javier Villanueva-Meyer, Tracy Luks, Yalan Zhang, Madhuri Kambhampati, Jie Zhang, Sridevi Yadavilli, Bo Zhang, Krutika S. Gaonkar, Jo Lynne Rokita, Adam Kraya, John Kuhn, Winnie Liang, Sara Byron, Michael Berens, Annette Molinaro, Michael Prados, Adam Resnick, Sebastian M. Waszak, Javad Nazarian, Sabine Mueller, University of Zurich, and Mueller, Sabine
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Cancer Research ,Clinical Trials and Supportive Activities ,Oncology and Carcinogenesis ,610 Medicine & health ,Astrocytoma ,Genomic Instability ,Circulating Tumor DNA ,Young Adult ,Rare Diseases ,Clinical Research ,Genetics ,Brain Stem Neoplasms ,Humans ,1306 Cancer Research ,Oncology & Carcinogenesis ,Child ,Biology ,Cancer ,Pediatric ,screening and diagnosis ,Human Genome ,Diffuse Intrinsic Pontine Glioma ,Neurosciences ,Glioma ,Brain Disorders ,4.1 Discovery and preclinical testing of markers and technologies ,Brain Cancer ,Detection ,Orphan Drug ,Good Health and Well Being ,Oncology ,10036 Medical Clinic ,2730 Oncology ,Female ,Biomarkers - Abstract
Purpose: PNOC003 is a multicenter precision medicine trial for children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG). Patients and Methods: Patients (3–25 years) were enrolled on the basis of imaging consistent with DIPG. Biopsy tissue was collected for whole-exome and mRNA sequencing. After radiotherapy (RT), patients were assigned up to four FDA-approved drugs based on molecular tumor board recommendations. H3K27M-mutant circulating tumor DNA (ctDNA) was longitudinally measured. Tumor tissue and matched primary cell lines were characterized using whole-genome sequencing and DNA methylation profiling. When applicable, results were verified in an independent cohort from the Children's Brain Tumor Network (CBTN). Results: Of 38 patients enrolled, 28 patients (median 6 years, 10 females) were reviewed by the molecular tumor board. Of those, 19 followed treatment recommendations. Median overall survival (OS) was 13.1 months [95% confidence interval (CI), 11.2–18.4] with no difference between patients who followed recommendations and those who did not. H3K27M-mutant ctDNA was detected at baseline in 60% of cases tested and associated with response to RT and survival. Eleven cell lines were established, showing 100% fidelity of key somatic driver gene alterations in the primary tumor. In H3K27-altered DIPGs, TP53 mutations were associated with worse OS (TP53mut 11.1 mo; 95% CI, 8.7–14; TP53wt 13.3 mo; 95% CI, 11.8–NA; P = 3.4e−2), genome instability (P = 3.1e−3), and RT resistance (P = 6.4e−4). The CBTN cohort confirmed an association between TP53 mutation status, genome instability, and clinical outcome. Conclusions: Upfront treatment-naïve biopsy provides insight into clinically relevant molecular alterations and prognostic biomarkers for H3K27-altered DIPGs.
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- 2022
23. Pathema: a clade-specific bioinformatics resource center for pathogen research.
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Lauren M. Brinkac, Tanja Davidsen, Erin Beck, Anuradha Ganapathy, Elisabet Caler, Robert J. Dodson, A. Scott Durkin, Derek M. Harkins, Hernan Lorenzi, Ramana Madupu, Yinong Sebastian, Susmita Shrivastava, Mathangi Thiagarajan, Joshua Orvis, Jaideep P. Sundaram, Jonathan Crabtree, Kevin Galens, Yongmei Zhao, Jason M. Inman, Robert Montgomery, Seth A. Schobel, Kevin Galinsky, David M. Tanenbaum, Adam Resnick, Nikhat Zafar, Owen White, and Granger G. Sutton
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- 2010
- Full Text
- View/download PDF
24. Does Offering Battlefield Acupuncture Lead to Subsequent Use of Traditional Acupuncture?
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Karleen F. Giannitrapani, Stephanie L. Taylor, Scott Coggeshall, Eva R Thomas, Steven B. Zeliadt, Adam Resnick, Hannah Gelman, Benjamin Kligler, and Juli Olson
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Research design ,Male ,Health Status ,Acupuncture, Ear ,Acupuncture Therapy ,8.1 Organisation and delivery of services ,Comorbidity ,0302 clinical medicine ,7.1 Individual care needs ,80 and over ,030212 general & internal medicine ,Veterans ,Aged, 80 and over ,education.field_of_study ,030503 health policy & services ,Pain Research ,Ear ,nonpharmacologic ,Battlefield Acupuncture ,Middle Aged ,United States Department of Veterans Affairs ,Mental Health ,Cohort ,Public Health and Health Services ,Health Policy & Services ,Regression Analysis ,Female ,Chronic Pain ,0305 other medical science ,Cohort study ,Health and social care services research ,Adult ,medicine.medical_specialty ,Adolescent ,Population ,Veterans Health ,03 medical and health sciences ,Young Adult ,Clinical Research ,Complementary and Integrative Health ,Acupuncture ,medicine ,Humans ,Pain Management ,acupuncture therapy ,education ,Propensity Score ,Aged ,auricular acupuncture ,business.industry ,Public Health, Environmental and Occupational Health ,Original Articles ,medicine.disease ,United States ,Good Health and Well Being ,Socioeconomic Factors ,Applied Economics ,complementary and integrative health ,Propensity score matching ,Physical therapy ,Management of diseases and conditions ,business - Abstract
Objectives: Veterans Health Administration encourages auricular acupuncture (Battlefield Acupuncture/BFA) as a nonpharmacologic approach to pain management. Qualitative reports highlighted a “gateway hypothesis”: providing BFA can lead to additional nonpharmacologic treatments. This analysis examines subsequent use of traditional acupuncture. Research Design: Cohort study of Veterans treated with BFA and a propensity score matched comparison group with a 3-month follow-up period to identify subsequent use of traditional acupuncture. Matching variables included pain, comorbidity, and demographics, with further adjustment in multivariate regression analysis. Subjects: We identified 41,234 patients who used BFA across 130 Veterans Health Administration medical facilities between October 1, 2016 and March 31, 2019. These patients were matched 2:1 on Veterans who used VA care but not BFA during the same period resulting in a population of 24,037 BFA users and a comparison cohort of 40,358 non-BFA users. Patients with prior use of traditional acupuncture were excluded. Results: Among Veterans receiving BFA, 9.5% subsequently used traditional acupuncture compared with 0.9% of non-BFA users (P
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- 2020
25. The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution
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Orit Rozenblatt-Rosen, Aviv Regev, Philipp Oberdoerffer, Tal Nawy, Anna Hupalowska, Jennifer E. Rood, Orr Ashenberg, Ethan Cerami, Robert J. Coffey, Emek Demir, Li Ding, Edward D. Esplin, James M. Ford, Jeremy Goecks, Sharmistha Ghosh, Joe W. Gray, Justin Guinney, Sean E. Hanlon, Shannon K. Hughes, E. Shelley Hwang, Christine A. Iacobuzio-Donahue, Judit Jané-Valbuena, Bruce E. Johnson, Ken S. Lau, Tracy Lively, Sarah A. Mazzilli, Dana Pe’er, Sandro Santagata, Alex K. Shalek, Denis Schapiro, Michael P. Snyder, Peter K. Sorger, Avrum E. Spira, Sudhir Srivastava, Kai Tan, Robert B. West, Elizabeth H. Williams, Denise Aberle, Samuel I. Achilefu, Foluso O. Ademuyiwa, Andrew C. Adey, Rebecca L. Aft, Rachana Agarwal, Ruben A. Aguilar, Fatemeh Alikarami, Viola Allaj, Christopher Amos, Robert A. Anders, Michael R. Angelo, Kristen Anton, Jon C. Aster, Ozgun Babur, Amir Bahmani, Akshay Balsubramani, David Barrett, Jennifer Beane, Diane E. Bender, Kathrin Bernt, Lynne Berry, Courtney B. Betts, Julie Bletz, Katie Blise, Adrienne Boire, Genevieve Boland, Alexander Borowsky, Kristopher Bosse, Matthew Bott, Ed Boyden, James Brooks, Raphael Bueno, Erik A. Burlingame, Qiuyin Cai, Joshua Campbell, Wagma Caravan, Hassan Chaib, Joseph M. Chan, Young Hwan Chang, Deyali Chatterjee, Ojasvi Chaudhary, Alyce A. Chen, Bob Chen, Changya Chen, Chia-hui Chen, Feng Chen, Yu-An Chen, Milan G. Chheda, Koei Chin, Roxanne Chiu, Shih-Kai Chu, Rodrigo Chuaqui, Jaeyoung Chun, Luis Cisneros, Graham A. Colditz, Kristina Cole, Natalie Collins, Kevin Contrepois, Lisa M. Coussens, Allison L. Creason, Daniel Crichton, Christina Curtis, Tanja Davidsen, Sherri R. Davies, Ino de Bruijn, Laura Dellostritto, Angelo De Marzo, David G. DeNardo, Dinh Diep, Sharon Diskin, Xengie Doan, Julia Drewes, Stephen Dubinett, Michael Dyer, Jacklynn Egger, Jennifer Eng, Barbara Engelhardt, Graham Erwin, Laura Esserman, Alex Felmeister, Heidi S. Feiler, Ryan C. Fields, Stephen Fisher, Keith Flaherty, Jennifer Flournoy, Angelo Fortunato, Allison Frangieh, Jennifer L. Frye, Robert S. Fulton, Danielle Galipeau, Siting Gan, Jianjiong Gao, Long Gao, Peng Gao, Vianne R. Gao, Tim Geiger, Ajit George, Gad Getz, Marios Giannakis, David L. Gibbs, William E. Gillanders, Simon P. Goedegebuure, Alanna Gould, Kate Gowers, William Greenleaf, Jeremy Gresham, Jennifer L. Guerriero, Tuhin K. Guha, Alexander R. Guimaraes, David Gutman, Nir Hacohen, Sean Hanlon, Casey R. Hansen, Olivier Harismendy, Kathleen A. Harris, Aaron Hata, Akimasa Hayashi, Cody Heiser, Karla Helvie, John M. Herndon, Gilliam Hirst, Frank Hodi, Travis Hollmann, Aaron Horning, James J. Hsieh, Shannon Hughes, Won Jae Huh, Stephen Hunger, Shelley E. Hwang, Heba Ijaz, Benjamin Izar, Connor A. Jacobson, Samuel Janes, Reyka G. Jayasinghe, Lihua Jiang, Brett E. Johnson, Bruce Johnson, Tao Ju, Humam Kadara, Klaus Kaestner, Jacob Kagan, Lukas Kalinke, Robert Keith, Aziz Khan, Warren Kibbe, Albert H. Kim, Erika Kim, Junhyong Kim, Annette Kolodzie, Mateusz Kopytra, Eran Kotler, Robert Krueger, Kostyantyn Krysan, Anshul Kundaje, Uri Ladabaum, Blue B. Lake, Huy Lam, Rozelle Laquindanum, Ashley M. Laughney, Hayan Lee, Marc Lenburg, Carina Leonard, Ignaty Leshchiner, Rochelle Levy, Jerry Li, Christine G. Lian, Kian-Huat Lim, Jia-Ren Lin, Yiyun Lin, Qi Liu, Ruiyang Liu, William J.R. Longabaugh, Teri Longacre, Cynthia X. Ma, Mary Catherine Macedonia, Tyler Madison, Christopher A. Maher, Anirban Maitra, Netta Makinen, Danika Makowski, Carlo Maley, Zoltan Maliga, Diego Mallo, John Maris, Nick Markham, Jeffrey Marks, Daniel Martinez, Robert J. Mashl, Ignas Masilionais, Jennifer Mason, Joan Massagué, Pierre Massion, Marissa Mattar, Richard Mazurchuk, Linas Mazutis, Eliot T. McKinley, Joshua F. McMichael, Daniel Merrick, Matthew Meyerson, Julia R. Miessner, Gordon B. Mills, Meredith Mills, Suman B. Mondal, Motomi Mori, Yuriko Mori, Elizabeth Moses, Yael Mosse, Jeremy L. Muhlich, George F. Murphy, Nicholas E. Navin, Michel Nederlof, Reid Ness, Stephanie Nevins, Milen Nikolov, Ajit Johnson Nirmal, Garry Nolan, Edward Novikov, Brendan O’Connell, Michael Offin, Stephen T. Oh, Anastasiya Olson, Alex Ooms, Miguel Ossandon, Kouros Owzar, Swapnil Parmar, Tasleema Patel, Gary J. Patti, Itsik Pe'er, Tao Peng, Daniel Persson, Marvin Petty, Hanspeter Pfister, Kornelia Polyak, Kamyar Pourfarhangi, Sidharth V. Puram, Qi Qiu, Álvaro Quintanal-Villalonga, Arjun Raj, Marisol Ramirez-Solano, Rumana Rashid, Ashley N. Reeb, Mary Reid, Adam Resnick, Sheila M. Reynolds, Jessica L. Riesterer, Scott Rodig, Joseph T. Roland, Sonia Rosenfield, Asaf Rotem, Sudipta Roy, Charles M. Rudin, Marc D. Ryser, Maria Santi-Vicini, Kazuhito Sato, Deborah Schrag, Nikolaus Schultz, Cynthia L. Sears, Rosalie C. Sears, Subrata Sen, Triparna Sen, Alex Shalek, Jeff Sheng, Quanhu Sheng, Kooresh I. Shoghi, Martha J. Shrubsole, Yu Shyr, Alexander B. Sibley, Kiara Siex, Alan J. Simmons, Dinah S. Singer, Shamilene Sivagnanam, Michal Slyper, Artem Sokolov, Sheng-Kwei Song, Austin Southard-Smith, Avrum Spira, Janet Stein, Phillip Storm, Elizabeth Stover, Siri H. Strand, Timothy Su, Damir Sudar, Ryan Sullivan, Lea Surrey, Mario Suvà, Nadezhda V. Terekhanova, Luke Ternes, Lisa Thammavong, Guillaume Thibault, George V. Thomas, Vésteinn Thorsson, Ellen Todres, Linh Tran, Madison Tyler, Yasin Uzun, Anil Vachani, Eliezer Van Allen, Simon Vandekar, Deborah J. Veis, Sébastien Vigneau, Arastoo Vossough, Angela Waanders, Nikhil Wagle, Liang-Bo Wang, Michael C. Wendl, Robert West, Chi-yun Wu, Hao Wu, Hung-Yi Wu, Matthew A. Wyczalkowski, Yubin Xie, Xiaolu Yang, Clarence Yapp, Wenbao Yu, Yinyin Yuan, Dadong Zhang, Kun Zhang, Mianlei Zhang, Nancy Zhang, Yantian Zhang, Yanyan Zhao, Daniel Cui Zhou, Zilu Zhou, Houxiang Zhu, Qin Zhu, Xiangzhu Zhu, Yuankun Zhu, and Xiaowei Zhuang
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Cell ,Genomics ,Computational biology ,Tumor initiation ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Metastasis ,03 medical and health sciences ,Atlases as Topic ,0302 clinical medicine ,Neoplasms ,Tumor Microenvironment ,medicine ,Humans ,Precision Medicine ,030304 developmental biology ,0303 health sciences ,Atlas (topology) ,Cancer ,medicine.disease ,3. Good health ,Human tumor ,Cell Transformation, Neoplastic ,medicine.anatomical_structure ,Single-Cell Analysis ,Single point ,030217 neurology & neurosurgery - Abstract
Crucial transitions in cancer-including tumor initiation, local expansion, metastasis, and therapeutic resistance-involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecedented resolution. The Human Tumor Atlas Network (HTAN), part of the National Cancer Institute (NCI) Cancer Moonshot Initiative, will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types. This effort complements both ongoing efforts to map healthy organs and previous large-scale cancer genomics approaches focused on bulk sequencing at a single point in time. Generating single-cell, multiparametric, longitudinal atlases and integrating them with clinical outcomes should help identify novel predictive biomarkers and features as well as therapeutically relevant cell types, cell states, and cellular interactions across transitions. The resulting tumor atlases should have a profound impact on our understanding of cancer biology and have the potential to improve cancer detection, prevention, and therapeutic discovery for better precision-medicine treatments of cancer patients and those at risk for cancer.
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- 2020
26. The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location
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Ilon Liu, Li Jiang, Erik R. Samuelsson, Sergio Marco Salas, Alexander Beck, Olivia A. Hack, Daeun Jeong, McKenzie L. Shaw, Bernhard Englinger, Jenna LaBelle, Hafsa M. Mire, Sibylle Madlener, Lisa Mayr, Michael A. Quezada, Maria Trissal, Eshini Panditharatna, Kati J. Ernst, Jayne Vogelzang, Taylor A. Gatesman, Matthew E. Halbert, Hana Palova, Petra Pokorna, Jaroslav Sterba, Ondrej Slaby, Rene Geyeregger, Aaron Diaz, Izac J. Findlay, Matthew D. Dun, Adam Resnick, Mario L. Suvà, David T. W. Jones, Sameer Agnihotri, Jessica Svedlund, Carl Koschmann, Christine Haberler, Thomas Czech, Irene Slavc, Jennifer A. Cotter, Keith L. Ligon, Sanda Alexandrescu, W. K. Alfred Yung, Isabel Arrillaga-Romany, Johannes Gojo, Michelle Monje, Mats Nilsson, and Mariella G. Filbin
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Genetics ,Ageing ,Cancer microenvironment ,CNS cancer ,Transcriptomics - Abstract
Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in diffuse midline gliomas (DMGs) of the childhood pons but are also increasingly recognized in adults. Their potential heterogeneity at different ages and midline locations is vastly understudied. Here, through dissecting the single-cell transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We show that stem-like oligodendroglial precursor-like cells, present across all clinico-anatomical groups, display varying levels of maturation dependent on location. We reveal a previously underappreciated relationship between mesenchymal cancer cell states and age, linked to age-dependent differences in the immune microenvironment. Further, we resolve the spatial organization of H3-K27M DMG cell populations and identify a mitotic oligodendroglial-lineage niche. Collectively, our study provides a powerful framework for rational modeling and therapeutic interventions.
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- 2021
27. Abstract 5268: The spectrum of FGFR mutations in pediatric and young adult solid tumor
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Jinhua Wu, Jeffrey Schubert, Feng Xu, Ariel Long, Maha Patel, Netta Golenberg, Weixuan Fu, Kajia Cao, Jiani Chen, Elizabeth H. Denenberg, Elizabeth A. Fanning, Rochelle Bagatell, Theodore W. Laetsch, Adam Resnick, Mariarita Santi, Phillip Jay B. Storm, Minjie Luo, Lea F. Surrey, Yiming Zhong, and Marilyn M. Li
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Cancer Research ,Oncology - Abstract
Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases expressed on the cell membrane that play crucial roles in cellular lineage commitment, differentiation, proliferation, and apoptosis. Deregulated FGFR signaling is observed in a subset of tumors across various histologies, making FGFRs ideal therapeutic targets. We sought to determine the genetic landscape of FGFR-family variations in a cohort of pediatric and young adult patients with solid tumors. The CHOP Comprehensive Solid Tumor Panel was performed on 1,420 patients. The panel covers 238 cancer genes and screens for single nucleotide variants (SNVs), indels, copy number alterations, and 117 fusion gene partners interrogating over 700 exons for known and novel fusions. Identified variants were categorized and reported according to the AMP/ASCO/CAP guidelines. Fifty-six patients (4.1%), including 47 children and 9 young adults, were found to carry at least one FGFR alteration in their tumors. CNS tumors accounted for most of the cases (51 total, 87.9%), with pilomyxoid astrocytoma/pilocytic astrocytoma and dysembryoplastic neuroepithelial tumor the most common (13 and 12 patients, respectively). Non-CNS solid tumors included rhabdomyosarcoma (4 patients), neuroblastoma/ganglioneuroblastoma (2), and follicular thyroid carcinoma (1). FGFR somatic alterations were found in 56 tumors including 41 SNVs and small indels, 6 internal tandem duplications (ITDs), and 15 fusions genes. The most common SNVs observed were hotspot mutations p.K656E and p.N546K of FGFR1. Sequence alterations in FGFR1 contained 35 SNVs and small indels, mostly gain of function mutations located in the kinase domain, and 6 kinase domain ITDs. One SNV was identified in FGFR2 in the immunoglobulin domain. Two SNVs were reported in FGFR3, both of which were in the fibroblast growth factor receptor family domain, and 3 SNVs were identified in FGFR4, all occurring at the p.V550 codon located on the kinase domain. Companion mutations in non-FGFR genes were detected in 27 tumors, predominantly involving RAS signaling pathway genes including NF1 (14 variants), PIK3CA (8), PTPN11 (6) and PIK3R1 (4). Among fusion variants, FGFR1-TACC1 fusions were found in 5 patients, mostly in pediatric patients. One FGFR3-TACC3 fusion was identified in one young adult patient. Seven pediatric patients tested positive for FGFR2 fusions; all with different 3’ partners. The detection of an FGFR alteration defined or changed the histologic diagnosis for 22 patients. Our results reveal that FGFR alterations account for 4.1% (56/1420) of the patients with solid tumors tested in our laboratory. The majority of the FGFR-positive tumors are low-grade CNS tumors. Further, the identification of FGFR alterations can significantly improve the tumor diagnosis and provide genomic evidence for potential targeted treatment with FGFR inhibitors. Citation Format: Jinhua Wu, Jeffrey Schubert, Feng Xu, Ariel Long, Maha Patel, Netta Golenberg, Weixuan Fu, Kajia Cao, Jiani Chen, Elizabeth H. Denenberg, Elizabeth A. Fanning, Rochelle Bagatell, Theodore W. Laetsch, Adam Resnick, Mariarita Santi, Phillip Jay B. Storm, Minjie Luo, Lea F. Surrey, Yiming Zhong, Marilyn M. Li. The spectrum of FGFR mutations in pediatric and young adult solid tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5268.
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- 2022
28. Abstract 1155: cBioPortal for cancer genomics
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Jianjiong Gao, Tali Mazor, Ino de Bruijn, Adam Abeshouse, Diana Baiceanu, Ziya Erkoc, Elena Garcia Lara, Benjamin Gross, David M. Higgins, Prasanna K. Jagannathan, Priti Kumari, Ritika Kundra, Xiang Li, James Lindsay, Aaron Lisman, Divya Madala, Ramyasree Madupuri, Angelica Ochoa, Oleguer Plantalech, Sander Rodenburg, Baby A. Satravada, Robert Sheridan, Lucas Sikina, Jessica Singh, S. Onur Sumer, Yichao Sun, Pim van Nierop, Avery Wang, Manda Wilson, Hongxin Zhang, Gaofei Zhao, Sjoerd van Hagen, Kees van Bochove, Ugur Dogrusoz, Allison Heath, Adam Resnick, Trevor J. Pugh, Chris Sander, Ethan Cerami, and Nikolaus Schultz
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Cancer Research ,Oncology - Abstract
cBioPortal for Cancer Genomics is an open-source platform for interactive, exploratory analysis of large-scale cancer genomics data sets. cBioPortal provides a user-friendly interface that integrates genomic and clinical data, and provides a suite of visualizations and analyses, including OncoPrints, mutation “lollipop” plots, variant interpretation, group comparison, survival analysis, expression correlation analysis, alteration enrichment analysis, cohort and patient-level visualization. cBioPortal also integrates external tools including CIViC, Cancer Digital Slide Archive, Next-Generation Clustered Heat Map, IGV and Bioconductor to facilitate interpretation. The public site (https://www.cbioportal.org) is accessed by ~35,000 unique visitors each month and hosts data from >325 studies spanning individual labs and large consortia. In addition, >67 instances of cBioPortal are installed at academic institutions and pharmaceutical/biotechnology companies worldwide. In 2021 we added data from 32 studies, totaling >24,000 samples, to the public site. All data is also available in the cBioPortal Datahub: https://github.com/cBioPortal/datahub/. We also host a dedicated instance for AACR Project GENIE, enabling access to the GENIE cohort of >135,000 clinically sequenced samples from 19 institutions (https://genie.cbioportal.org). In addition, the GENIE Biopharma Collaborative (BPC) enables the collection of comprehensive clinical annotations, including response, outcome, and treatment histories. The first BPC release contains data from >1,800 non-small cell lung cancer samples and will be released in early 2022. The growing GENIE cohort and the BPC clinical data have driven a number of recent developments, including performance improvements (the load time for the GENIE cohort was reduced from minutes to seconds). To leverage the BPC clinical data, we enabled sample selection based on treatment status, extended support for outcome analysis, and enhanced the patient timeline representation to incorporate response data. Additional development work has focused on improvements to variant interpretation, enhancements to the Mutations tab, and support for novel molecular assays via the ‘generic assay’ data type. Documentation on these new features and many others is available at https://www.cbioportal.org/news. cBioPortal is fully open source (https://github.com/cBioPortal/) under a GNU Affero GPL license. Development is a collaborative effort among groups at Memorial Sloan Kettering Cancer Center, Dana-Farber Cancer Institute, Children’s Hospital of Philadelphia, Princess Margaret Cancer Centre, Bilkent University and The Hyve. We welcome open source contributions from others in the cancer research community. Citation Format: Jianjiong Gao, Tali Mazor, Ino de Bruijn, Adam Abeshouse, Diana Baiceanu, Ziya Erkoc, Elena Garcia Lara, Benjamin Gross, David M. Higgins, Prasanna K. Jagannathan, Priti Kumari, Ritika Kundra, Xiang Li, James Lindsay, Aaron Lisman, Divya Madala, Ramyasree Madupuri, Angelica Ochoa, Oleguer Plantalech, Sander Rodenburg, Baby A. Satravada, Robert Sheridan, Lucas Sikina, Jessica Singh, S. Onur Sumer, Yichao Sun, Pim van Nierop, Avery Wang, Manda Wilson, Hongxin Zhang, Gaofei Zhao, Sjoerd van Hagen, Kees van Bochove, Ugur Dogrusoz, Allison Heath, Adam Resnick, Trevor J. Pugh, Chris Sander, Ethan Cerami, Nikolaus Schultz. cBioPortal for cancer genomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1155.
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- 2022
29. OTHR-43. Composition of cell-free miRNA in cerebrospinal fluid and plasma as a monitoring tool for pediatric brain tumors
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Coyle Anne, Madison Hollawell, Komal Rathi, Christopher Beck, Namrata Choudhari, Tiffany Smith, Madsen Peter, Phillip Storm, Adam Resnick, Jessica Foster, and Mateusz Koptyra
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Cancer Research ,Oncology ,Neurology (clinical) - Abstract
Current clinical management of pediatric brain tumor patients involves non-invasive imaging studies to monitor therapeutic response and tumor progression. However, results are often inconclusive and unable to capture biological changes that presage progression on imaging. Non-invasive diagnostics, also termed liquid biopsy, have emerged for detection of cell-free cancer material but there are no such standard, clinically defined biomarkers or methods for pediatric brain tumors. Circulating miRNA presents an attractive biomarker platform given its stability in bio-fluids, selective expression in tumors and release from tumor cells into the extracellular environment. Technology development has permitted high throughput analysis of material obtained from biofluids including plasma and cerebrospinal fluid (CSF). We performed miRNA profiling across a cohort of 54 pediatric brain tumors from different histologies (low grade glioma, ependymoma, germinoma, medulloblastoma, atypical teratoid rhabdoid tumor and high-grade glioma) using CSF (33) and plasma (53) with HTG EdgeSeq platform. CSF and plasma specimens clustered independently of each other providing separate biomarker platforms. Consensus clustering performed on CSF specimens revealed clusters correlated with disease severity (tumor grade). We identified miRNA targets closely correlated with tumor grade (p
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- 2022
30. IMMU-22. Safely targeting GD2 in thalamic diffuse midline glioma with mRNA CAR T cells
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Jessica Foster, Crystal Griffin, Allison Stern, Peter Madsen, Phillip Storm, and Adam Resnick
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Cancer Research ,Oncology ,Neurology (clinical) - Abstract
Chimeric antigen receptor (CAR) T cells targeting the disialoganglioside GD2 have shown promise as a therapeutic for diffuse midline glioma (DMG). However, prior studies raised significant concerns of neurotoxicity and fatality when using virally transduced CAR T cells against midline thalamic tumors. Building upon our prior work optimizing mRNA for use in CAR T cells (Hum Gen Ther, 2019), we hypothesized repeated dosing of transient GD2-directed mRNA CAR T cells could be employed for safe and effective treatment of thalamic DMG. GD2-directed CAR T cells were created using mRNA encoding the 14G2a single chain variable fragment paired with 41BB and CD3-zeta co-stimulatory domains and transfected into human T cells. CAR T cells were tested against the murine thalamic DMG xenograft 7316-6349 via locoregional delivery with an indwelling infusion catheter for repeated dosing. The previously reported fatal neurotoxicity observed in mice using lentiviral CAR T cells could be recapitulated with aggressive dosing. Four doses of 5 x 106 mRNA CAR T cells delivered intratumorally twice a week resulted in median overall survival of 9 days for GD2-treated mice compared to >30 days for CD19-treated controls (p
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- 2022
31. HGG-54. CLK1 aberrant splicing in pediatric high-grade gliomas disrupts key oncogenic transcriptional programs
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Ammar Naqvi, Brian Ennis, Run Jin, Krutika Gaonkar, Jessica Foster, Karina Conkrite, Komal Rathi, Adam Kraya, Poonam Sonawane, Peter Madsen, Phillip Storm, Adam Resnick, and Jo Lynne Rokita
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Cancer Research ,Oncology ,Neurology (clinical) - Abstract
While much of the somatic coding variation underlying the oncogenic transformation of pediatric high-grade gliomas (HGGs) has been profiled, transcriptional splicing programs of these tumors remain under-explored. Here, we characterize aberrant alternative splicing in pediatric midline HGGs (n = 84). We identified 19,275 recurrent and significant (20% change from control, P < 0.05, FDR < 0.05) aberrant splicing events in 8,587 genes compared to non-diseased brainstem controls. Of those, 27% (n = 5,157) resulted in either a gain or loss of a known protein functional site within 3,294 genes. We prioritized splice variants affecting targetable kinases and found that mRNAs encoding CDC-like kinase 1 (CLK1), a known modulator of master splicing regulators, exhibit significantly increased exon 4 inclusion in midline HGGs. This leads to a gain of two known phosphorylation sites in CLK1, increased CLK1 protein expression and hyper-phosphorylation of Serine-rich splicing factors. To assess the impact of this event, we performed differential splicing and expression analyses, comparing tumors with the highest (n= 5) and lowest (n = 5) exon 4 inclusion. We discovered 3,037 genes to be differentially up-regulated in high exon 4 inclusion tumors with an enrichment of cancer-related pathways, including DNA repair, mitotic spindle, myogenesis and EMT. We next integrated these gene signatures with protein-protein interaction networks of kinase and transcription factors and show that increased CLK1 exon 4 inclusion disrupts critical regulatory networks, such as those involving FOXM1, which is implicated in cell cycle and proliferation processes. In summary, we describe aberrant splicing in pediatric HGGs as an additional mechanism that could drive tumorigenesis. Future work will focus on molecular validation and therapeutic targeting of CLK1 in available HGG models. Characterizing tumor-specific splicing variation has the potential to open new therapeutic strategies and understand mechanisms of treatment resistance in children with central nervous system tumors.
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- 2022
32. EPCT-08. Disease-specific working groups within the Pacific Pediatric Neuro-Oncology Consortium (PNOC) and Children’s Brain Tumor Network (CBTN) facilitate multi-disciplinary collaboration and translation of innovative strategies in pediatric neuro-oncology
- Author
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Cassie Kline, Adam Resnick, Michael Prados, and Sabine Mueller
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Cancer Research ,Oncology ,Neurology (clinical) - Abstract
BACKGROUND: In Summer 2019, PNOC leadership developed working groups to align basic scientists, clinical researchers, and foundations for rapid translation of novel therapies for children and young adults with central nervous system tumors. Soon after, PNOC partnered with the Children’s Brain Tumor Network (CBTN) to grow collaborations and augment preclinical resources. Since their inception, working groups have advanced translation of new therapies and biomarkers, developed pipelines for preclinical and clinical research, and expanded global collaborations. DESIGN: Each working group is led by 2 to 3 experts in a disease, such as medulloblastoma, diffuse midline glioma, or craniopharyngioma, or subject matter, like imaging, nursing, or diversity, equity, and inclusion. A project manager coordinates regular multidisciplinary meetings to share new findings from research laboratories, provide updates on clinical trial development (with real-time feedback and incorporation of trial endpoints and biomarkers), and invite speakers to share advancements in the disease or subject of interest. RESULTS: Eleven working groups have been created with over 200 members across the United States, Europe, Australia. More than 20 foundations, led predominantly by families, provide support and insight to guide working group efforts. Working groups have developed 4 clinical trials (n=2, diffuse midline glioma; n=1, craniopharyngioma; n=1, medulloblastoma) and completed 3 international surveys, investigating experiences of patients/families affected by craniopharyngioma, evaluating diversity and inclusion throughout the consortia, and assessing nursing and advanced practice provider needs. Additional accomplishments include a registry for atypical teratoid rhabdoid tumors, a population dataset evaluating diversity in clinical research participation across consortia, incorporation of nursing members for review and refinement of clinical trial protocols, and updated imaging case report forms for application across clinical trials. CONCLUSION: Multidisciplinary working groups within international consortia facilitate efficient translation of multi-pronged strategies to improve the care of children and young adults with central nervous system tumors.
- Published
- 2022
33. DIPG-31. Prognostic and predictive biomarkers of response in children and young adults with H3K27M-altered diffuse intrinsic pontine glioma: results from a multi-center, interventional clinical trial (PNOC003)
- Author
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Cassie Kline, Payal Jain, Lindsay Kilburn, Erin Bonner, Nalin Gupta, John Crawford, Anu Banerjee, Roger Packer, Javier Villanueva-Meyer, Tracy Luks, Yalan Zhang, Madhuri Kambhampati, Jie Zhang, Sridevi Yadavilli, Adam Kraya, John Kuhn, Winnie Liang, Sara Byron, Michael Berens, Annette Molinaro, Michael Prados, Adam Resnick, Sebastian Waszak, Javad Nazarian, and Sabine Mueller
- Subjects
Cancer Research ,Oncology ,Neurology (clinical) - Abstract
BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is a fatal brain tumor. Herein, we report on novel prognostic and predictive genomic biomarkers identified in PNOC003, a multi-center precision medicine trial for children and young adults diagnosed with DIPG. METHODS: Patients aged 3-25 years were enrolled on PNOC003 based on radiographic diagnosis of DIPG. Pre-treatment tumor biopsies were analyzed using tumor-normal whole-exome sequencing and mRNA-tumor sequencing to determine biology-informed, multi-agent therapy following radiation therapy (RT). Whole-genome sequencing was performed as an exploratory study aim. Genomic biomarkers were investigated to identify predictors of RT response and overall survival (OS) in patients with confirmed H3K27M-altered DIPG. Prognostic biomarkers were verified in a retrospective, H3K27M-altered diffuse midline glioma cohort (n=22) from the Children’s Brain Tumor Network (CBTN). RESULTS: Thirty patients enrolled on PNOC003 met molecular criteria for H3K27M-altered DIPG. TP53 was the most frequently altered driver gene (73%). Somatic alterations in PTEN>TP53>PDGFRA were independently associated with OS (P
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- 2022
34. TBIO-11. The glutamine transporter and candidate diagnostic and therapeutic target SLC1A5 is associated with subtype-specific metabolic phenotypes and tumor prognosis in pediatric brain cancers
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Adam Kraya, Run Jin, Chao Zhao, Ariana Familiar, Kathryn Wellen, Adam Resnick, and Ali Nabavizadeh
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Cancer Research ,Oncology ,Neurology (clinical) - Abstract
Glutamine transporters play an important role in supporting increased tumor nutritional demands relative to non-cancerous cells, often through overexpression of the solute carrier (SLC) family of membrane transporters. Preclinical studies in adult cancers demonstrate that targeting glutamine addiction via SLC1A5 inhibition results in growth-inhibitory and tumoricidal effects. Given their relatively higher expression in cancer versus normal brain tissue, SLC transporters represent compelling targets for molecularly-targeted radiation and application of available prognostic amino-acid PET imaging probes. However, the role of SLC transporters in pediatric brain cancers has yet to be investigated. We aimed to understand the relationship of SLC transporter expression with pediatric brain tumor subtypes and their potential prognostic significance using data from the Pediatric Brain Tumor Atlas (PBTA). Using the expression of amino acid transporter genes in ensemble survival models (Reactome: R-HSA-352230), we found that elevated expression of glutamine transporters (SLC1A5, SLC7A5, SLC7A11, SLC38A5, SLC38A3) predicted shorter progression-free survival (PFS) in low-grade gliomas (LGGs) and poorer overall survival in pediatric ependymomas, high-grade gliomas (HGGs), and medulloblastomas. We focused specifically on SLC1A5 given the availability of imaging probes (18 F-Fluoroglutamine and 18F-Fluciclovine) for the corresponding amino acid transporter (ASCT2). Through transcriptome-based consensus clustering, we found that supratentorial, RELA fusion-positive ependymomas and sonic hedgehog-activated medulloblastomas were over-represented among clusters expressing higher levels of SLC1A5 (p = 3.38e-7 and p = 2.18-26, respectively). Kaplan-Meier analysis found that higher expression of SLC1A5 was associated with shorter OS in ependymoma and medulloblastoma (p = 9.8e-4 and p = 0.032) and shorter PFS in LGG (p = 0.022). Gene set analysis showed higher expression and network rewiring of amino acid, lipid, and immune pathways in SLC1A5-high expressing clusters. Our work demonstrates that glutamine transporters, particularly SLC1A5, represent compelling targets in pediatric brain cancers that warrant further investigation for molecularly-targeted treatment and amino-acid PET imaging.
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- 2022
35. RARE-13. Clinical management and functional and survival outcomes in pediatric craniopharyngioma, a patient and family perspective
- Author
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Emily Marshall, Sylvia Cheng, Julia Crowley, Shana McCormack, Brian Rood, Todd Hankinson, Michael DeCuypere, Sandy Lam, Stewart Goldman, Svenja Boekhoff, Hermann L Muller, Ryan Velasco, Phillip B Storm, Adam Resnick, Michael Prados, Sabine Mueller, Cassie Kline, and Fatema Malbari
- Subjects
Cancer Research ,Oncology ,Neurology (clinical) - Abstract
Craniopharyngiomas are rare, histologically benign, sellar/parasellar tumors with significant tumor and therapy related morbidity and impairment in quality of life (QOL). We report survey results from patients/families affected by childhood-onset craniopharyngioma to identify opportunities for improvement in management. An anonymous REDCap survey was distributed via social media and clinic visits to patients/families of craniopharyngioma survivors. Survey questions investigated perspectives on clinical management and functional and survival outcomes at initial diagnosis and recurrence. A total of 159 patients/families completed the survey, 40% (n=64) reported craniopharyngioma recurrence. For primary craniopharyngioma, maximal safe resection was the most frequent treatment reported (n=84), followed by partial resection (n=40), radiation (n=8), biopsy (n=5), and chemotherapy (n=3). Most patients (n=120) decided on a treatment plan within one week, 63 (40%) decided in one day. For recurrent craniopharyngioma, maximal safe resection and radiation were the most frequent interventions (n=33 each), followed by partial resection (n=13), chemotherapy (n=4) and biopsy (n=2). Multiple treatment options and/or participation in a clinical trial were offered to similar numbers of patients across primary and recurrent diagnoses (~21% for each). Most recurrent craniopharyngioma patients decided on management within one week (n=43). Long term effects related to tumor and treatment were identified as the primary concern in all respondents. The most common deficits for all patients were neuro-endocrine followed by vision and neurocognition problems. Neuro-endocrine complications were self-reported as the biggest impact on QOL. Families reported that they would prefer treatment options with the potential for improved QOL, even if these options also carried an increased risk of recurrence. Craniopharyngioma continues to be predominantly treated with surgery and radiation initially and with recurrence. Survivors have multiple comorbidities, with an interest in targeted therapies that preserve QOL. Novel therapies to prevent co-morbidities and provide long term benefits are necessary and upcoming.
- Published
- 2022
36. MODL-17. The Childhood Brain Cancer Cell Line Atlas: A Resource for Biomarker Identification and Therapeutic Development
- Author
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Paul Daniel, Claire Sun, Mateusz Koptyra, Caroline Drinkwater, Nicole Chew, Gabrielle Bradshaw, Melissa Loi, Claire Shi, Motahhareh Tourchi, Sarah Parackal, Wai Chin Chong, Dasun Fernando, Shazia Adjumain, Hoang Nguyen, Dilru Habarakada, Dhanya Sooraj, Duncan Crombie, Nataliya Zhukova, Chris Jones, Jeffrey Rubens, Eric Raabe, Maria Vinci, Matt Dun, Louise Ludlow, Javad Nazarian, Jamie Fletcher, Paul Ekert, David Ziegler, Amos Hong Pheng Loh, Sharon Yin Yee Low, Michelle Monje, Naama Neeman, Bryan Williams, Adam Resnick, Daniel Gough, Jason Cain, and Ron Firestein
- Subjects
Cancer Research ,Oncology ,Neurology (clinical) - Abstract
Cell lines represent the most versatile and widely used models of cancer and, as such, are critical for identifying and advancing new therapies. Strikingly, there is a significant gap in both the number of childhood brain cancer cell lines and their characterisation compared to their adult counterparts. To address this inequity, we established a childhood brain cancer cell line atlas (publicly available at vicpcc.org.au/dashboard) encompassing over 180 childhood CNS-derived cell lines, representing 20 tumour types and 11 molecular subtypes. Cell lines are characterized by whole genome, RNA-sequencing, phospho- and total proteomics, DNA methylation and ATAC-seq analyses. Multi-omic factor analysis revealed distinct lineage-specified classification of our cell line cohort. In parallel, high throughput drug and CRISPR/Cas9 screens were conducted to map the functional dependencies in over 70 childhood CNS cell lines, including 47 paediatric high grade glioma models. These screens identified both lineage and molecular-subtype specific genetic and drug dependencies, underscoring the utility of this wide-scale approach. Machine based learning approaches to predict genotype-phenotype correlations uncovered distinct paediatric-specific biomarkers of growth dependency, highlighting the unique genetic wiring underlying paediatric CNS tumours. Finally, by integrating functional, molecular and drug profiles of paediatric CNS cell lines, we construct a system to prioritize investigation of novel therapeutic target-biomarkers pairs in specific CNS tumour types.
- Published
- 2022
37. OTHR-45. Kids First Variant WorkBench: application to germline genomic discoveries in the Children's Brain Tumor Network
- Author
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Yiran Guo, Jeremy Costanza, Christophe Botek, Miguel Brown, David Higgins, Yuankun Zhu, Bailey Farrow, Allison Heath, Adam Resnick, and Vincent Ferretti
- Subjects
Cancer Research ,Oncology ,Neurology (clinical) - Abstract
The Gabriella Miller Kids First Pediatric Research Program (Kids First) aims at facilitating researchers to uncover new insights into the biology of childhood cancer (CC) and structural birth defects (SBD). Kids First has two initiatives, i) whole genome sequencing of biospecimens from families with CC/SBD, and ii) establishing Kids First Data Resources. Kids First Data Resource Center developed the Kids First Data Resource Portal (KFDRP), a centralized platform to search, view, analyze, and identify currently accessible data from both Kids First and collaborative cohorts, incorporating omics and phenotypic information of 30 studies and 26,300 participants. A recently released KFDRP component is Variant WorkBench (VWB), enabling users to query, mangle, analyze and visualize genomic variants from participating cohorts, with the Children’s Brain Tumor Network (CBTN) being one of the cohorts. VWB supports programming languages such as Python, Spark, SQL and R for in-depth analysis in Apache Zeppelin notebooks. In addition to variant calls and phenotypic information, VWB hosts rich external variant annotations in the public domain, such as Cancer Hotspots, COSMIC and ClinVar. Users can also load additional databases (e.g. Human Gene Mutation Database/HGMD) within a notebook, import custom datasets as temporary query tables, export analysis outputs to local drives, visualize analysis results in multiple chart styles, display local figures, and save notebooks for sharing, further use and Cavatica projects. In an effort to screen tier 1 genes (n=578) from the most recent Cancer Gene Census provided by COSMIC in CBTN, we identified ~127,500 germline variants that are both rare and damaging, or that are already cataloged in the most recent version of ClinVar/HGMD. The whole process took less than one hour which is much faster than conventional methods. VWB enables efficient genomic variant analysis and discoveries in pediatric neuro-oncology research with advanced big data technology.
- Published
- 2022
38. Laser beam propagation simulations of long-path scintillation and fade with comparison to ground-to-aircraft optical link measurements
- Author
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Yousef K. Chahine, Gunnar Ristroph, Rani Megally, Alex Hsia, John Malowicki, Adam C. Wroblewski, Adam Resnick, and Joseph M. Flatico
- Subjects
Physics ,Scintillation ,business.industry ,Optical link ,Optical engineering ,General Engineering ,Optical communication ,Spectral density ,Atmospheric model ,Atomic and Molecular Physics, and Optics ,Optics ,Fade ,business ,Atmospheric optics - Abstract
An analysis of optical scintillation and fade on long slant-path atmospheric channels is presented via a direct comparison between wave-optics-based numerical simulations and experimental flight data from a ground-to-aircraft optical communication link. In addition to physically modeling the propagation through slant-path atmospheric turbulence, the numerical simulations include simultaneously the effects of mechanical pointing jitter, aperture-averaging, and first-order scattering/absorption models. The power spectral density, fade probability, and mean fade time of the simulated power fluctuations are studied and validated against measurements taken at slant-path distances ranging from 60 to 113 km and aircraft speeds up to 70 m / s.
- Published
- 2021
39. Abstract 207: the cBioPortal for cancer genomics
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Jianjiong Gao, Tali Mazor, Ino de Bruijn, Adam Abeshouse, Diana Baiceanu, Ziya Erkoc, Benjamin Gross, David Higgins, Prasanna K. Jagannathan, Karthik Kalletla, Priti Kumari, Ritika Kundra, Xiang Li, James Lindsay, Aaron Lisman, Pieter Lukasse, Divya Madala, Ramyasree Madupuri, Angelica Ochoa, Oleguer Plantalech, Joyce Quach, Sander Rodenburg, Anusha Satravada, Fedde Schaeffer, Robert Sheridan, Lucas Sikina, S. Onur Sumer, Yichao Sun, Paul van Dijk, Pim van Nierop, Avery Wang, Manda Wilson, Hongxin Zhang, Gaofei Zhao, Sjoerd van Hagen, Kees van Bochove, Ugur Dogrusoz, Allison Heath, Adam Resnick, Trevor J. Pugh, Chris Sander, Ethan Cerami, Nikolaus Schultz, and Doğrusöz, Uğur
- Subjects
Cancer Research ,Oncology - Abstract
The cBioPortal for Cancer Genomics is an open-source software platform that enables interactive, exploratory analysis of large-scale cancer genomics data sets with a user-friendly interface. It integrates genomic and clinical data, and provides a suite of visualization and analysis options, including OncoPrint, mutation diagram, variant interpretation, survival analysis, expression correlation analysis, alteration enrichment analysis, cohort and patient-level visualization, among others. The public site (https://www.cbioportal.org) hosts data from almost 300 studies spanning individual labs and large consortia. Data is also available in the cBioPortal Datahub (https://github.com/cBioPortal/datahub/). In 2020 we added data from 21 studies, totaling almost 30,000 samples. In addition, we added data to existing TCGA PanCancer Atlas studies, including MSI status, mRNA-seq z-scores relative to normal tissue, microbiome data, and RPPA-based protein expression. The cBioPortal also supports AACR Project GENIE with a dedicated instance hosting the GENIE cohort of 112,000 clinically sequenced samples from 19 institutions worldwide (https://genie.cbioportal.org). The site is accessed by over 30,000 unique visitors per month. To support these users, we hosted a five-part instructional webinar series. Recordings of these webinars are available on our website and have already been viewed thousands of times. In addition, more than 50 instances are installed at academic institutions and pharmaceutical/biotechnology companies. In support of these local instances, we continue to simplify the installation process: we now provide a docker compose solution which includes all microservices to run the web app as well as data validation, import and migration. We continue to enhance and expand the functionality of cBioPortal. This year we significantly enhanced the group comparison feature; it is now integrated into gene-specific queries and supports comparison of more data types including DNA methylation, microbiome, and any outcome measure. We also expanded support of longitudinal data: the existing patient timeline has been refactored and now supports a wider range of data and visualizations; a new “Genomic Evolution” tab highlights changes in mutation allele frequencies across multiple samples from a patient; and samples can now be selected based on pre- or post-treatment status. Other features released this year include: allowing users to add gene-level plots for continuous molecular profiles in study view, enabling users to select the desired transcript on the Mutations tab, and integration of PathwayMapper. The cBioPortal is fully open source (https://github.com/cBioPortal/) under a GNU Affero GPL license. Development is a collaborative effort among groups at Memorial Sloan Kettering Cancer Center, Dana-Farber Cancer Institute, Children's Hospital of Philadelphia, Princess Margaret Cancer Centre, Bilkent University and The Hyve. Citation Format: Jianjiong Gao, Tali Mazor, Ino de Bruijn, Adam Abeshouse, Diana Baiceanu, Ziya Erkoc, Benjamin Gross, David Higgins, Prasanna K. Jagannathan, Karthik Kalletla, Priti Kumari, Ritika Kundra, Xiang Li, James Lindsay, Aaron Lisman, Pieter Lukasse, Divya Madala, Ramyasree Madupuri, Angelica Ochoa, Oleguer Plantalech, Joyce Quach, Sander Rodenburg, Anusha Satravada, Fedde Schaeffer, Robert Sheridan, Lucas Sikina, S. Onur Sumer, Yichao Sun, Paul van Dijk, Pim van Nierop, Avery Wang, Manda Wilson, Hongxin Zhang, Gaofei Zhao, Sjoerd van Hagen, Kees van Bochove, Ugur Dogrusoz, Allison Heath, Adam Resnick, Trevor J. Pugh, Chris Sander, Ethan Cerami, Nikolaus Schultz. The cBioPortal for Cancer Genomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 207.
- Published
- 2021
40. DDRE-12. PNOC001 (NCT01734512): A PHASE II STUDY OF EVEROLIMUS FOR RECURRENT OR PROGRESSIVE PEDIATRIC LOW-GRADE GLIOMAS (pLGG)
- Author
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Sabine Mueller, Mariam Aboian, Kellie Nazemi, Karen Gauvain, Janet Yoon, Jane Minturn, Sarah Leary, Mohamed AbdelBaki, Stewart Goldman, Jennifer Elster, Adam Resnick, Annette Molinaro, Joanna Phillips, Michael Prados, and Daphne Haas-Kogan
- Subjects
Cancer Research ,Oncology ,Drug Discovery, Drug Resistance ,Neurology (clinical) - Abstract
OBJECTIVE To estimate the 6-month Progression Free Survival (PFS6) associated with everolimus for progressive/recurrent pLGGs and to determine if activated PI3K/Akt/mTOR pathway as measured by positive phosphorylated-ribosomal protein S6 (p-RPS6) status was associated with response. METHOD Patients 3–21 years of age with recurrent or progressive pLGG were enrolled. Everolimus was administered orally at 5 mg/m2 daily. Tissue availability for molecular analysis was mandatory. Immunohistochemistry (IHC) for p-RPS6 was performed centrally. An adaptive Simon two-stage design was employed based on p-RPS6 status. Based on results of the first stage, enrollment in the second stage was either limited to pathway activated patients or open to all subjects. RESULTS From December 2012 to July 2019 a total of 65 subjects enrolled [median age 9 years (range 3–19); 43% female]. As of December 15, 2019 median number of treatment cycle is 8 (range 1–24); 7 patients remain on treatment. Toxicity profile is similar to published reports with rash and elevated lipid profiles as most common adverse events. PFS6 for the entire cohort is 63%; PFS6 is 64% for the activated and 61% for the non-activated patients. Central imaging review (n=52) revealed 1 partial response, 1 complete response, 33 stable disease, and 17 progressive disease at the end of study treatment. Initial molecular analysis identified BRAF alterations in 35/65 patients. CONCLUSION Everolimus is well tolerated and active in a subset of pLGGs. Ongoing analyses will assess predictive biomarkers of response and will be reported at the meeting.
- Published
- 2020
41. Abstract PO-116: Identifying disparities across race, ethnicity, and gender in pediatric neuro-oncology clinical research - from patient to provider
- Author
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Emily Marshall, Tom Belle Davidson, Jeffrey Stevens, Kristina Cole, Fatema Malbari, Tabitha Cooney, Lance Ballaster, Kaitlin Lehmann, Shannon Robins, Miguel Brown, Christopher Blackden, Christopher Friedman, Ammar Naqvi, Jonathan Waller, Ximena Cueller, Jennifer Mason, Jena Lilly, Phillip Jay B Storm, Adam Resnick, Michael Prados, Sabine Mueller, Angela Waanders, and Cassie Kline
- Subjects
Oncology ,Epidemiology - Abstract
Background: Literature has shown that racial, ethnic, and gender disparities exist among clinical research participants and within the ranks of academic institutions. To assess this and develop solutions to potential disparities in pediatric neuro-oncology, the Pacific Pediatric Neuro-Oncology Consortium (PNOC) and Children's Brain Tumor Network (CBTN) Diversity, Equity, and Inclusion (DEI) working group distributed a survey to all members of the consortia regarding the state of DEI in our research environments. In parallel, the working group collated clinical data from a public CBTN dataset and a PNOC clinical trial patient cohort to assess racial, ethnic, and gender differences in clinical research participation and outcomes. Methods: This study consisted of two components: an electronically distributed REDCap survey of all PNOC and CBTN consortia members (distributed Fall 2020) and analysis of pediatric neuro-oncology patient cohorts from CBTN and PNOC. The survey collected demographic information of respondents and Likert opinions on DEI at the consortia- and institution level (e.g. “All team members are treated fairly”). Responses were then stratified based on self-identified race, ethnicity, and gender and by age and job title. Patient-level data from the CBTN and PNOC cohorts was collated to evaluate overall patient demographics and clinical outcomes stratified by race, ethnicity, and gender and including differences in survival and clinical research enrollment. Outcomes: Fifty-seven PNOC/CBTN members initiated survey responses, with 45 completing the entire survey (estimated 20-25% response rate). Responders were predominantly white, non-hispanic females with the most common age range of 35-44 years and with faculty or physician job titles, followed by clinical research staff. Statistically significant differences were identified in questions related to the DEI environment mainly at the institution-level. Regarding feelings of inclusion, acceptance, and fair treatment, distinctions were identified across self-reported race and gender with white race correlating with higher frequency of feeling included and respected and females most commonly reporting neutral or disagreement that all team members are treated fairly and that different cultures and backgrounds are valued and interact well. At the patient level, the CBTN and PNOC data pulls included 1711 and 463 patients, respectively, with analyses currently underway and to be aligned with data from the Central Brain Tumor Registry of the United States (CBTRUS) to assess for race, ethnicity, gender, and locoregional differences in our patient cohort and in the context of national registry data. Conclusions: The experiences and feelings of inclusion and treatment of clinical research members within the clinical research environment of pediatric neuro-oncology differ based on self-identified race and gender. Investigation is in process to extrapolate patient-level differences across race, ethnicity, and gender and in the context of larger registry data for pediatric neuro-oncology. Citation Format: Emily Marshall, Tom Belle Davidson, Jeffrey Stevens, Kristina Cole, Fatema Malbari, Tabitha Cooney, Lance Ballaster, Kaitlin Lehmann, Shannon Robins, Miguel Brown, Christopher Blackden, Christopher Friedman, Ammar Naqvi, Jonathan Waller, Ximena Cueller, Jennifer Mason, Jena Lilly, Phillip Jay B Storm, Adam Resnick, Michael Prados, Sabine Mueller, Angela Waanders, Cassie Kline. Identifying disparities across race, ethnicity, and gender in pediatric neuro-oncology clinical research - from patient to provider [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-116.
- Published
- 2022
42. Clinical efficacy and predictive biomarkers of ONC201 in H3 K27M-mutant diffuse midline glioma
- Author
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Carl Koschmann, Abed Rahman Kawakibi, Rohinton Tarapore, Sharon Gardner, Chase Thomas, Rodrigo Cartaxo, Viveka Yadav, Andrew Chi, Sylvia Kurz, Patrick Wen, Isabel Arrillaga, Tracy Batchelor, Nicholas Butowski, Ashley Sumrall, Nicole Shonka, Rebecca Harrison, John De Groot, Minesh Mehta, Yazmin Odia, Matthew Hall, Doured Daghistani, Timothy Cloughesy, Benjamin Ellingson, Michelle Kim, Yoshie Umemura, Hugh Garton, Andrea Franson, Patricia Robertson, Jonathan Schwartz, Bernard Marini, Manjunath Pai, Timothy Phoenix, Sunjong Ji, Evan Cantor, Zachary Miklja, Brendan Mullan, Amy Bruzek, Ruby Siada, Jessica Cummings, Stefanie Stallard, Kyle Wierzbicki, Alyssa Paul, Ian Wolfe, Matthew Dun, Jason Cain, Li Jiang, Mariella Filbin, Pankaj Vats, Chandan Kumar-Sinha, Rajen Mody, Arul Chinnaiyan, Drew Pratt, Sriram Venneti, Guangrong Lu, Sabine Mueller, Adam Resnick, Javad Nazarian, Sebastian Waszak, and Joshua Allen
- Abstract
Patients with diffuse midline glioma (DMG) harboring H3 K27M mutation have no proven therapies beyond radiation. ONC201, a DRD2 antagonist and mitochondrial ClpP agonist, has induced early responses in patients with H3 K27M-mutant DMG. We performed an integrated pre-clinical and clinical assessment of ONC201 treatment, in order to define response rates in H3 K27M-mutant DMG patients and to clarify predictors of response. ONC201 was effective in murine H3 K27M-mutant gliomas with excellent CNS penetration and survival benefit. H3 K27M-mutant DMG patients treated with ONC201 on active clinical trials (n=50) showed significant survival benefit in recurrent and non-recurrent settings, with multiple sustained responses. Tumor sequencing from treated patients demonstrates an EGFR/FOXG1-driven telencephalic gene regulatory network that imparts a critical resistance phenotype to ONC201. Genetic and pharmacologic knockdown of EGFR in H3 K27M-mutant cell cultures results in improved sensitivity to ONC201 and reduced FOXG1 enhancer binding, suggesting possible future combinatorial opportunities.
- Published
- 2020
43. Recovery in the U.S. Virgin Islands: Progress, Challenges, and Options for the Future
- Author
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Howard Shatz, Patrick Roberts, Adam Resnick, Susan Resetar, Benjamin Preston, Shanthi Nataraj, Kristin Leuschner, Andrew Lauland, Cynthia Cook, Joie Acosta, Blas Nunez-Neto, and Shelly Culbertson
- Published
- 2020
44. Accelerating learning healthcare system development through embedded research: Career trajectories, training needs, and strategies for managing and supporting embedded researchers
- Author
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Elizabeth M. Yano, Michael Gluck, Adam Resnick, Kamila B. Mistry, and Harry Kwon
- Subjects
Program evaluation ,Knowledge management ,business.industry ,Health Policy ,Health services research ,Stakeholder engagement ,Learning Health System ,Career Pathways ,Research Personnel ,03 medical and health sciences ,Leadership ,0302 clinical medicine ,Brainstorming ,Health care ,Workforce ,Humans ,030212 general & internal medicine ,Curriculum ,business ,Psychology ,030217 neurology & neurosurgery ,Career development - Abstract
Background Health systems and organizations seeking to achieve learning healthcare system principles are increasingly relying on embedded research teams to optimize delivery of evidence-based, high-quality care that improves patient and staff experience alike. However, building organizational capacity to conduct and benefit from embedded research may be challenging in the absence of clearer guidance on career pathways and training, as well as strategies for managing and supporting this unique workforce. Methods In February 2018, 115 attendees from multiple agencies, institutions and professional societies participated in a conference to accelerate development of learning healthcare systems through embedded research. Workgroups engaged in structured brainstorming discussions of key domains; 21 diverse members focused on strengthening the embedded research community through more explicit development and support of multilevel career trajectories. Results Emphasis emerged on the need for training that goes beyond traditional curricula in rigorous scientific methods to include leadership, communication, and other organizational and business skills rarely offered in research training programs. These skills are required for effective engagement of multilevel stakeholders supporting evidence-based changes in routine care. Improving readiness of other stakeholders to effectively act on evidence was noted as equally crucial, as was creation of mid-career development opportunities for researchers and implementers. Conclusions Further development and support of the embedded research workforce will require explicit attention to novel training programs and support of researchers and the stakeholders in the systems they aim to improve. Implications Strategies for improving career entry and mastery of skills that foster effective multilevel stakeholder engagement hold promise for strengthening the embedded research community and their contributions to systematic improvements in health and health care.
- Published
- 2019
45. Health Outcomes Associated With Smoke Exposure in Albuquerque, New Mexico, During the 2011 Wallow Fire
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Brian Woods, Heidi Krapfl, Barbara Toth, and Adam Resnick
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Adult ,Male ,Gerontology ,Adolescent ,New Mexico ,Population ,Poison control ,Fires ,Occupational safety and health ,Disasters ,symbols.namesake ,Outcome Assessment, Health Care ,Injury prevention ,Humans ,Medicine ,Poisson regression ,Child ,education ,Aged ,Asthma ,education.field_of_study ,business.industry ,Health Policy ,Public Health, Environmental and Occupational Health ,Environmental Exposure ,Emergency department ,Middle Aged ,Smoke Inhalation Injury ,medicine.disease ,Confidence interval ,Cross-Sectional Studies ,Child, Preschool ,symbols ,Female ,Emergency Service, Hospital ,business ,Demography - Abstract
OBJECTIVE: This study examined the association between PM2.5 levels and emergency department (ED) visits for selected health outcomes in Albuquerque, New Mexico, during the Wallow fire of 2011. DESIGN: Measurements of 24-hour average concentrations of PM2.5 obtained from the City of Albuquerque were used to calculate wildfire smoke exposure in Albuquerque. Daily ED visits were collected by the New Mexico Department of Health from individual nonfederal licensed facilities in the Albuquerque area. Poisson regression was used to assess the relationship between ED visits for selected respiratory and cardiovascular conditions and varying levels of PM2.5 exposure. SETTING: Albuquerque, New Mexico. PARTICIPANTS: Patients visiting an ED for select conditions before, during, and after the wildfire. MAIN OUTCOME MEASURE: Relative increase in ED visits for selected conditions during the wildfire period. RESULTS: Analysis of PM2.5 exposure data and ED visits in Albuquerque before and during the Wallow fire indicated that compared with the period prior to the fire, there was an increased risk of ED visits for some respiratory and cardiovascular conditions during heavy smoke conditions, and risk varied by age and sex. The population of 65+ years was especially at risk for increased ED visits. There was a significantly increased risk of ED visits among the 65+ population for asthma (RR [relative rate] = 1.73, 95% confidence interval [CI] = 1.03-2.93) and for diseases of the veins, lymphatic and circulatory system (RR = 1.56, 95% CI = 1.00-2.43). For the age group of 20 to 64 years, there was a statistically significant increase in ED visits for diseases of pulmonary circulation (RR = 2.64, 95% CI = 1.42-4.9) and for cerebrovascular disease (RR = 1.69, 95% CI = 1.03-2.77). CONCLUSIONS: High levels of PM2.5 exposure due to the Wallow fire were associated with increased ED visits for respiratory and cardiovascular conditions in Albuquerque. More effective and targeted preventive measures are necessary to reduce morbidity rates associated with wildfire smoke exposure among vulnerable populations. Language: en
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- 2015
46. Data Commons to Support Pediatric Cancer Research
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Samuel L. Volchenboum, Suzanne M. Cox, Allison Heath, Adam Resnick, Susan L. Cohn, and Robert Grossman
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03 medical and health sciences ,Neuroblastoma ,0302 clinical medicine ,Biomedical Research ,Databases, Factual ,030225 pediatrics ,030220 oncology & carcinogenesis ,Humans ,General Medicine ,Child ,Medical Oncology - Abstract
The falling costs and increasing fidelity of high-throughput biomedical research data have led to a renaissance in cancer surveillance and treatment. Yet, the amount, velocity, and complexity of these data have overcome the capacity of the increasing number of researchers collecting and analyzing this information. By centralizing the data, processing power, and tools, there is a valuable opportunity to share resources and thus increase the efficiency, power, and impact of research. Herein, we describe current data commons and how they operate in the oncology landscape, including an overview of the International Neuroblastoma Risk Group data commons as a paradigm case. We outline the practical steps and considerations in building data commons. Finally, we discuss the unique opportunities and benefits of creating a data commons within the context of pediatric cancer research, highlighting the particular advantages for clinical oncology and suggested next steps.
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- 2017
47. The Effects of Travel and Tourism on California's Economy: A Labor Market--Focused Analysis
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Adam Resnick, Olena Bogdan, Edward Keating, and Matthew Baird
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- 2017
48. Abstract 2465: Genomic harmonization of the Data Resource Center for Gabriella Miller Kids First Pediatric Research Program
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Yuankun Zhu, Miguel Brown, Batsal Devkota, Bailey Farrow, Bogdan Gavrilovic, Allison Heath, Kyle Hernandez, Avi Kelman, Parimala Killada, Meen Chul Kim, Daniel Kolbman, Mateusz Koptyra, Milan Kovacevic, Maarten Leerkes, Alex Lubneuski, Michele Mattioni, Pichai Raman, Adam Resnick, Nikola Skundric, Deanne Taylor, Junjun Zhang, Bo Zhang, and Phillip B. Storm
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Cancer Research ,Oncology - Abstract
Gabriella Miller Kids First Pediatric Research Program (GMKF) is a nation-wide, multi-year initiative focused on the integration of large-scale clinically annotated genomic data for childhood cancers and structural birth defects supported by the NIH Common Fund. Awarded by GMKF, the Kids First Data Resource Center (DRC) is tasked to build infrastructure and workflows for data intaking, harmonization, integration and access authorization to empower collaborative discoveries across the GMKF and other integrated datasets. A key challenge for uniform analyses and empowered discovery of large-scale genomic data relates to the diverse genomic processing workflows and methods employed across the sequencing and bioinformatics community. The DRC genomic harmonization team aims to provide “analysis ready” datasets that are “functionally equivalent” across the Kids First datasets and other large-scale genomic data initiatives in order to accelerate the discovery process. Paired with the cloud-based workspace environments of the DRC, such harmonized dataset provide unprecedented opportunities for shared, reproducible discovery by a diverse, collaborative network of researchers. As such, DRC initial pipelines are developed with BWA-MEM alignment on genome build GRCh38 followed by the GATK best practices for germline variant calling and joint genotyping. Common Workflow Language (CWL) is used as the main workflow specification, while Docker technology has been applied to containerize all the tools used by the workflow. Our current workflows are tasked with data harmonization across a number of different experimental platforms including whole genome sequencing, exome sequencing, and RNA-seq. The data processing is done via CAVATICA, an Amazon Web Services (AWS) based cloud computing platform associated with the Kids First DRC Portal co-developed by Seven Bridges Genomics, where workflows feature scatter-gather parallelization and AWS resource optimization. By utilizing such a framework, the DRC team has harmonized over 10,000 WGS and 1,000 RNA-Seq samples across 12 study cohorts within 8 months. This dataset in its current release includes samples from 40 pediatric brain cancers as well as 8 childhood birth defects with the outcome of delivering 150TB harmonized CRAM and 60TB gVCF. With a highly optimized bioinformatics pipeline powered by an efficient cloud-based execution workflow, The DRC platform processes one genome in about 11 hours with an average compute cost of $15 for whole genome alignment and germline variant calling. Here we present our observed challenges and identified opportunities in the analysis and integration of multi-disease pediatric genomic data on a large scale. Citation Format: Yuankun Zhu, Miguel Brown, Batsal Devkota, Bailey Farrow, Bogdan Gavrilovic, Allison Heath, Kyle Hernandez, Avi Kelman, Parimala Killada, Meen Chul Kim, Daniel Kolbman, Mateusz Koptyra, Milan Kovacevic, Maarten Leerkes, Alex Lubneuski, Michele Mattioni, Pichai Raman, Adam Resnick, Nikola Skundric, Deanne Taylor, Junjun Zhang, Bo Zhang, Phillip B. Storm. Genomic harmonization of the Data Resource Center for Gabriella Miller Kids First Pediatric Research Program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2465.
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- 2019
49. Abstract 910: The cBioPortal for cancer genomics
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Jianjiong Gao, Tali Mazor, Adam Abeshouse, Ersin Ciftci, Ino de Bruijn, Benjamin Gross, Karthik Kalletla, Priti Kumari, Ritika Kundra, James Lindsay, Aaron Lisman, Pieter Lukasse, Ramyasree Madupuri, Angelica Ochoa, Oleguer Plantalech, Pichai Raman, Fedde Schaeffer, Robert Sheridan, Jing Su, S. Onur Sumer, Yichao Sun, Sander Tan, Sjoerd van Hagen, Avery Wang, Manda Wilson, Hongxin Zhang, Gaofei Zhao, Kelsey Zhu, Kees van Bochove, Ugur Dogrusoz, Trevor J. Pugh, Adam Resnick, Chris Sander, Ethan Cerami, and Nikolaus Schultz
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Cancer Research ,Oncology - Abstract
The cBioPortal for Cancer Genomics is an open-source software platform that enables interactive, exploratory analysis of large-scale cancer genomics data sets with a biologist-friendly interface. It integrates genomic and clinical data, and provides a suite of visualization and analysis options, including OncoPrint, mutation diagram, variant interpretation, survival analysis, expression correlation analysis, alteration enrichment analysis, cohort and patient-level visualization, among others. The public site (http://www.cbioportal.org) hosts data from more than 200 studies from individual labs and large consortia, including the newly added TCGA Pan-Cancer Atlas data and the Count Me In project. These studies can be explored and queried individually or combined together into “virtual studies”. Users are now allowed to login and save virtual studies for query and analysis. The site is currently accessed by approximately 30,000 unique visitors per month. The software is also installed locally at dozens of academic institutions and pharmaceutical/biotechnology companies. A notable instance is the cBioPortal for AACR GENIE (http://www.cbioportal.org/genie/) hosting 60,000 clinically sequenced samples from multiple institutions. Over the past year, the code base has been fully refactored, resulting in a more responsive and interactive website. A new web API is in beta facilitating easier programmatic access to data. In addition, all public studies are available for download from the new datahub (https://github.com/cBioPortal/datahub/). The cBioPortal remains under active development. The portal is fully open source (https://github.com/cBioPortal/) under a GNU Affero GPL license. Development is a collaborative effort among groups at Memorial Sloan Kettering Cancer Center, Dana-Farber Cancer Institute, Children’s Hospital of Philadelphia, Princess Margaret Cancer Centre, and The Hyve. Ongoing and future development is focused on: (1) building the open source community; (2) continued performance improvements; (3) expanding user support, documentation and training resources; (4) developing novel features to support immunogenomics and immunotherapy; (5) enhancing individual variants and overall patient interpretation; (6) creating a simplified query interface; and (7) enabling comparative analysis of user-defined patient cohorts. Citation Format: Jianjiong Gao, Tali Mazor, Adam Abeshouse, Ersin Ciftci, Ino de Bruijn, Benjamin Gross, Karthik Kalletla, Priti Kumari, Ritika Kundra, James Lindsay, Aaron Lisman, Pieter Lukasse, Ramyasree Madupuri, Angelica Ochoa, Oleguer Plantalech, Pichai Raman, Fedde Schaeffer, Robert Sheridan, Jing Su, S. Onur Sumer, Yichao Sun, Sander Tan, Sjoerd van Hagen, Avery Wang, Manda Wilson, Hongxin Zhang, Gaofei Zhao, Kelsey Zhu, Kees van Bochove, Ugur Dogrusoz, Trevor J. Pugh, Adam Resnick, Chris Sander, Ethan Cerami, Nikolaus Schultz. The cBioPortal for cancer genomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 910.
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- 2019
50. Abstract 3356: Working together to put kids first: Outreach strategies driving collaborative research, data sharing and cross-disease analysis to accelerate discoveries in pediatric cancer and structural birth defects
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Tatiana S. Patton, Robert Moulder, Erin Alexander, Donna Vito, Jonathan Waller, Colleen Gaynor, Sarah Thomas, Bailey Farrow, Joseph Yamada, Kim Cullion, Danyelle Winchester, Angela Waanders, Allison Heath, Pichai Raman, Adam Resnick, and Jena Lilly
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Cancer Research ,Oncology - Abstract
The Gabriella Miller Kids First Pediatric Research Program launched the Kids First Pediatric Data Resource Center (DRC) in 2017 as a collaborative, pediatric research effort with the goal of understanding the genetic causes of and links between childhood cancer and structural birth defects. The DRC is charged with developing data-driven platforms that integrate large amounts of genomic and clinical data, empowering the collaborative discovery, engagement, and necessary partnerships that are crucial for progress in our biological understanding of diseases, enabling rapid translation to personalized treatments for patients and accelerating discovery of genetic causes and shared biologic pathways within and across these conditions. The DRC is comprised of 3 cores including the Data Resource Portal Core, Data Coordination Core and the Administrative & Outreach Core (AOC). The AOC brings together researchers, physicians, and patient and foundation advocates to support collaborative research and data sharing to accelerate discoveries. The AOC specific aims are to employ outreach strategies including print, web, social media, in-person presentations, conferences, videos, webinars, e-newsletters, surveys, communication strategies, and reports to support accelerated discoveries. The AOC is committed to learning from the childhood cancer and birth defect communities. By capturing, synthesizing, and prioritizing unmet needs for development of the Kids First DRC portal, website, and materials, the AOC engages with researchers, clinicians, foundations, and patient advocates in the childhood cancer and structural birth defect communities. In its first year, the AOC partnered with 32 foundations to launch the Kids First DRC Portal and support data sharing throughout the research community. Key findings during the first six months of requirements gathering revealed the following unmet needs: a) Increase understanding of the disease types, research projects, and the investigators that are a part of the Kids First community b) Highlight the need for cross-disease analyses including structural birth defects and childhood cancers and c) Promote education on the data sharing, agreements, data availability and accessibility. The AOC, gathered pertinent user requirements, conducted educational activities, and engaged prospective users of the researcher community resulting in over 200 users and 22,000 portal views since launch and will continue to use feedback from the research community to further inform the development of the Kids First DRC tools and materials to meet the goals of the program. Citation Format: Tatiana S. Patton, Robert Moulder, Erin Alexander, Donna Vito, Jonathan Waller, Colleen Gaynor, Sarah Thomas, Bailey Farrow, Joseph Yamada, Kim Cullion, Danyelle Winchester, Angela Waanders, Allison Heath, Pichai Raman, Adam Resnick, Jena Lilly. Working together to put kids first: Outreach strategies driving collaborative research, data sharing and cross-disease analysis to accelerate discoveries in pediatric cancer and structural birth defects [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3356.
- Published
- 2019
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