Search

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.

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.

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.

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.

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.

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.

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.

Childhood cancers and structural birth defects share a common context of altered developmental biology, but the potential role of shared, genetic alterations and/or pathways across pediatric cancers and birth defects is not well explored. It is increasingly critical that genomic data are paired with high-quality clinical data to drive translational research by elucidating the relationship between genomic alterations, treatments, outcomes, and other phenotypic characteristics. The NIH Common Fund Gabriella Miller Kids First Program represents a first-in-kind national, collaborative initiative focused on large-scale clinical and genomic data sharing for childhood cancers and structural birth defects. As part of this program, the Kids First Data Resource Center (DRC) is charged with empowering collaborative discovery across Kids First datasets. Through newly developed cloud-based platforms, researchers will be able to rapidly and interactively access standardized and harmonized clinical and genomic data. A better understanding of common developmental programs could spur advancements in prevention, detection, and therapeutics that will improve the outcomes of affected children and families. Approximately 8,000 patient samples were available at the launch of the Kids First DRC portal, with an initial focus on whole genome sequencing (WGS) of trios and families. More than 25,000 WGS are expected to be processed by 2019, making the DRC one of the largest pediatric data resources of its kind across a diversity of diseases. The rise of cloud-based computing has greatly reduced the burden on the researcher of large-scale genomic harmonization. In normal operations, the DRC is capable of running two hundred workflows simultaneously with considerable scalability on demand. Additionally, there is a strong focus on harmonizing and structuring seemingly disparate clinical and phenotypic data types to make them more interoperable, discoverable and reusable by using ontologies. The data in the DRC is expertly curated and mapped to existing data standards, including NCI Thesaurus (NCIt), Human Phenotype Ontology (HPO), Monarch Disease Ontology (MONDO), and Uber-anatomy Ontology (Uberon). This allows for increased interoperability and semantic structure of the data. For example, MONDO integrates numerous disease terminologies into a single merged ontology, including the NCIt. The combination of harmonized genomic and clinical data across pediatric cancers and structural birth defect provides a key foundation for exploring and developing new methods to better understand the relationships between germline variants, cancer risk, and associated treatments and outcomes. Community standardization of this modeling is ongoing as part of GA4GH, and is critical for implementation of improved interpretation in EHR systems, for example via HL7 FHIR. Citation Format: Allison P. Heath, Deanne M. Taylor, Yuankun Zhu, Pichai Raman, Jena Lilly, Phillip Storm, Angela J. Waanders, Vincent Ferretti, Christina Yung, Michele Mattioni, Brandi Davis-Dusenbery, Zachary L. Flamig, Robert Grossman, Samuel L. Volchenboum, Sabine Mueller, Javad Nazarian, Nicole Vasilevsky, Melissa A. Haendel, Adam Resnick. Gabriella Miller Kids First Data Resource Center: Harmonizing clinical and genomic data to support childhood cancer and structural birth defect research [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 2464.

Craniopharyngiomas are epithelial tumors that typically arise in the suprasellar region of the brain. Patients experience substantial clinical sequelae both from extension of the tumors and from therapeutic interventions which damage the optic chiasm, the pituitary stalk, and the hypothalamic area. Using whole exome sequencing we identified mutations in beta-catenin (CTNNB1) in nearly all adamantinomatous craniopharyngiomas (11/12; 92%) and recurrent mutations in BRAF (V600E) in all papillary craniopharyngiomas (3/3; 100%). Targeted genotyping revealed BRAF V600E in 95% of papillary craniopharyngiomas (36 of 39 tumors) and CTNNB1 mutation in 96% of adamantinomatous craniopharyngiomas (51 of 53 tumors). The CTNNB1 and BRAF mutations were clonal in each tumor subtype and no other recurrent mutations or genomic aberrations were detected in either subtype. Adamantinomatous and papillary craniopharyngiomas harbor mutations that are mutually exclusive and clonal. These findings have important implications for the diagnosis and treatment of these neoplasms. Citation Format: Amaro N. Taylor-Weiner, Priscilla K. Brastianos, Peter E. Manley, Robert T. Jones, Dora Dias-Sangata, Aaron Thorner, Fausto Rodriguez, Lindsay Bernardo, Laura Schubert, Chip Stewart, Mark Keiran, William C. Hahn, Adam Resnick, David Louis, Sandro Sangata, Gad Getz. Exome sequencing reveals BRAF mutations in papillary craniopharyngiomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 935. doi:10.1158/1538-7445.AM2014-935