CBTN specimen will be used for reduced representation bisulfite sequencing - we will be profiling the transcriptome and epigenome. We will then compare these profiles between boys and girls with pediatric GBM to identify lesions that cause the difference in clinical outcomes of these patients.

For this project, tumors of the specific histologic diagnoses of neurocytoma with or without matching blood specimens in the repository were identified for the whole-genome and RNA sequencing.

This project aims to validate a novel RNA analysis platform. FFPE tissue material will be processed by the HTG EdgeSeq technology pipeline for mRNA and/or miRNA profiling.The HTG EgdeSeq system is an automated chemistry and workflow solution based on the HTG Molecular Diagnostics’ (HTG) ex

Cancers commonly arise as the result of changes affecting the DNA sequence of cells including single nucleotide variations, small insertions and deletions, and structural variations including deletions, duplications, inversions, and translocations. In addition to these, cancer specific splicing a

The Comparative Oncology Trials Consortium at the National Cancer Institute have been performing canine glioma pre-clinical trials to evaluate therapeutic strategies for human and canine benefit. However, the similarity between human and canine glioma at the molecular and genomic level is unknown

Primary brain tumors are remarkably diverse, with more than 100 different defined types. This large diversity of brain tumors approximates the diversity of cell types in the normal brain, suggesting that each type of brain tumor corresponds to a different cell of origin transformed by a particula

Adamantiomatious Craniopharyngioma (ACP) is a benign intracranial tumor that is thought to arise from embryonic remnants of Rathke’s pouch. Though histologically benign, the clinical manifestation of the disease is profound due to the location of the tumor in the sellar/parasellar region around c

Ependymoma is the third most common brain tumour of childhood, and current treatments are limited to surgery and radiation even in very young children. Both supratentorial and posterior fossa ependymoma are relatively chemotherapy resistant, and patients with relapsed or subtotally resected disea

Low-grade gliomas are the most prevalent brain cancer among children. While patients with this type of cancer respond well to surgery, the majority experience recurrence after initial resection, requiring additional rounds of treatment that are rarely guided by molecular information. Intra-tumour

Scientists at Children’s Medical Research Institute are analysing tens of thousands of examples of all types of cancer from all over the world to develop a library of information to advance scientific discovery and enhance clinical treatment worldwide.This database will mean doctors can ef

Atypical Teratoid Rhabdiod Tumor (ATRT) is a pediatric central nervous system tumor. ATRT accounts for about 2% of pediatric CNS tumors, however it accounts for 20% of CNS tumors in children less than 3 years old (1). Overall survival for patients diagnosed with ATRT is a dismal 10-17 months, and

Pediatric High-grade glioma with H3K27M mutation (H3K27M-pHGG) carries an average overall survival of 1-2 years, and new targeted therapies are needed urgently. ONC201 is a dopamine receptor (DRD2) antagonist that is effective against H3K27M-pHGGs in pre-clinical and anecdotal clinical (case repo

The knowledge of the pathways and target genes that can drive tumors into less recurrent/progressive and rather sensitive to treatment can be a key for cancer treatment. To achieve this, we need to understand heterogeneity within the cancer cells and the cell clones that survive treatment and/or

The Schnepp laboratory focuses on aggressive solid tumors including high-risk neuroblastoma, and rhabdomyosarcoma. Compared to adult tumors, these have few somatic mutations that can be targeted, suggesting the need to identify additional druggable targets. Previous work in the lab has identified

Because the immune system can suppress and even eradicate tumor growth, tumor progression in central nervous system (CNS) tumors has been linked to immune evasion strategies. The capability of the immune system to recognize and inhibit the growth of cancer is dependent on its ability to recognize

Medulloblastoma is the most common malignant pediatric brain tumor. Current therapies consist of surgical resection, whole brain or spinal cord radiation or aggressive chemotherapy. While five year survival in pediatric patients rates at 60-70%, survivors face neurological, intellectual, and phys

Medulloblastoma (MB) is the most common pediatric brain tumor arising in the cerebellum. MBs are classified as WHO grade IV tumors and are highly malignant tumors commonly metastasizing to sites in the surrounding brain and spinal cord regions via cerebrospinal fluid (CSF), and in rare cases of e

Brain tumors are rare and when combined with other nervous system tumors account for ~ 2% of all cancers; however, they are the second most common type of pediatric cancer and the leading cause of childhood cancer-related mortality. The etiology and molecular features of most pediatric brain tumo

Medulloblastoma is the most common childhood cancer in the brain. Despite recent advances in therapeutic outcomes the survival rate of medulloblastoma patients is reaching plateau levels. Based on gene expression analysis, medulloblastomas are divided into four subgroups, the SHH (Sonic Hedgehog)

Tumor biomarkers (TB) that are validated surrogate endpoints of a drug's therapeutic effect can improve the accuracy and sensitivity of assessing tumor response in phase 2 trials and could also substantially shorten the time line of phase 3 trials if they are predictive of subsequent relapse

Our proposal develops an exciting new approach known as oncolytic virus. It is a remarkable fact that some common viruses (e.g. measles, poliovirus) preferentially infect and kill tumor cells. This fact was discovered at the beginning of the 20th century. However, it was not until recently that t

One of the challenges in neuro-oncology, which is particularly germane to the pediatric population, is the lack of robust biomarkers that can be used to monitor disease burden. The primary modality for diagnosing disease onset, persistence or progression is radiographic imaging with computed tomo

Pediatric brain tumors are the leading cause of disease related death in children. Major factors contributing to treatment failures for children with brain tumors include: a) the lack of comprehensive molecular characterization involving integration of the DNA-RNA-protein profiling; b) comprehens

Medulloblastoma (MB) is the most common malignant brain tumor in children. Despite aggressive tumor treatment, a significant proportion of MB patients still succumbs to this devastating disease. Improved strategies to treat MB can only come from deeper understandings of molecular and cellular bas

Children with brain tumors such as medulloblastoma continue to have poor outcomes despite maximal intensification of existing radiation and chemotherapeutic regimens. Consistent with their embryonal origins, medulloblastomas and other brain tumors differentially express lineage-specific cell surf

Medulloblastoma is a malignancy of the cerebellum, and is the most common pediatric brain tumor. The heterogeneity displayed by the tumors of these patients has been largely reconciled with the current molecular classifications which stratify tumors into four subgroups: WNT, SHH, Group 3, and Gro

The goal of this project is to determine patterns of tumor-specific protein expression in tumor tissue and cerebrospinal fluid (CSF) collected from children with glioma and normal controls using novel proteomics techniques. Expression patterns of specific proteins known as histones will be correl

Ependymoma is the third most common brain tumor of childhood, and can occur anywhere in the nervous system. Although classically described as a single entity, it is now very clear that different compartments of ependymoma are totally different diseases, specifically the supratentorial, posterior

Ependymomas constitute nearly one third of the central nervous system neoplasms among children aged < 3 years1. The disease remains a significant therapeutic challenge, with a 5-year overall survival rate < 55 % among this age group2 and no available chemotherapy of proven efficacy. The bre

Development of targeted therapy against ependymomas has been hampered by the lack of robust preclinical models. In addition, earlier genomic profiling of ependymomas failed to identify recurrent mutations in these tumors. With the discovery of the recurrent C11orf95/RELA translocation in supraten

Spinal ependymomas (SEs) are rare tumors of the central nervous system with limited treatment options and poor outcomes for more advanced disease. Successful treatment depends primarily upon complete surgical resection of the tumor, which is generally feasible only for well-differentiated (Grade

Medulloblastoma is the most common malignant brain tumor in children under 18 years of age. It is classified as World Health Organization (WHO) grade IV. Four different subgroups of medulloblastomas—WNT, SHH, Group 3, and Group 4—have been identified based on molecular characteristics. Today, med

Pediatric high-grade astrocytoma (pHGA), which diffusely infiltrates the brain, is the main cause of brain tumor death in children, with near 100% fatality. A lack of targeted therapies and pediatric-specific pre-clinical models contribute to this poor survival. Sequencing efforts, by us and othe

DIPG and ATRT are epigeneitcally driven diseases with poor outcomes. New therapies are desperately needed. The lack of drugable mutations and intra and intertumoral heterogeneity as well as the cancer stem cell characteristics of these tumors are barriers to target identification and deployment o

Pediatric high grade glioma (pHGG) remains a fatal disease with no cure in sight. Missense somatic mutations affecting histone H3.3 proteins are now accepted as the hallmark of pediatric diffuse intrinsic pontine gliomas (DIPG) and non-brain stem pHGG. However, little is known about the mechanist

In most children who are diagnosed with brain tumors, the underlying cause is unknown. It is likely that in many cases, inherited DNA mutations cause pediatric brain tumors, but researchers have been able to find such evidence for relatively few pediatric brain tumors; thus there is an urgent nee

Our understanding of molecular pathogenesis of cancer has increased over the years and as a result personalized treatments became available. More recently pharmaceutics leading to changes in epigenetic landscape gained attention as a promising targeted treatment, mostly to support other cancer th

High grade pediatric brain tumors (pHGG) are a devastating disease with a median survival of only 9-15 months. Importantly, pHGG represent the greatest cause of cancer related death in children under 19 years of age even though the overall incidence is low (1.78/100,000). In recent years it has b

Oligodendroglioma is a primary malignant brain cancer that develops from oligodendrocytes. Oligodendroglioma is one of the more common types of glioma (which also includes glioblastoma multiforme and astrocytoma). It is a rare tumor that strikes people of all ages; on average, 1,500 new cases are

Gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNET) are the most frequently identified tumors in epilepsy surgical series, yet their molecular determinants are poorly understood. Their characteristic histopathological features, together with the coexistence with cortical dyspla

We are investigating whether pediatric brain tumors (pHGGs, DIPGs) display intratumoral genetic heterogeneity, and the relationship between germline and somatic events as they relate to the clonal evolution of the disease.

Our overall objective of the project is the implementation of single-cell sequencing techniques in the context of a multiomics approach that includes bulk WGS, RNAseq, and total/phospho proteomics to investigate pediatric and AYA HGG biology. Analyses will focus on biospecimens collected across m

Meningioma and schwannoma are intracranial nervous system tumors that are predominantly benign in behavior arise through mutation and loss of function in the Neurofibromatosis type 2 (NF2) gene. Meningioma is the most common primary brain tumor and has a variable risk of local recurrence.O

The goal of the Center for Pediatric Tumor Cell Atlas (CPTCA) is to molecularly characterize the genome, transcriptome, methylome and chromatin accessibility at critical transition points in 3 deadly pediatric cancers: pediatric high grade glioma (pHGG), high risk neuroblastoma (HR NB) and very h

Childhood brain cancer is a devastating disease that is still poorly understood. Glioma is a type of brain cancer in which a specific type of cells in the brain (called glial cells), become cancerous. In our study, we will examine how the DNA in glioma cells varies between different groups of pat

Different tumors have different types of immune responses. We would like to better understand the drivers of this differential response so that we can best treat these tumors.

Pediatric high grade gliomas are molecularly different from adult gliomas and in comparison to adults, children with high grade gliomas have persistently poor clinical outcomes. Molecular markers have been shown to be important for treatment of adult gliomas, and new molecular markers for pediatr

We are evaluating expression of genes that are deferentially expressed by the effect of specific gene mutations. Especially, as the first step, we are evaluating immune-response related genes that are up-regulated or down-regulated in gliomas with H3K27M mutations. Our goal is to better understan

We plan to identify genes that are up- and down-regulated in brain tumors compared to normal tissue samples and genes that are up- and down-regulated in brain tumors with different mutations. We will compare these patient-derived gene expression profiles to data we have generated using human brai

Patients diagnosed with high-grade pediatric brain tumors have long-term survival rates of only 10 - 15% despite aggressive treatments with surgery and irradiation. To address this grim prognosis, cancer immunotherapy, a strategy whereby the host immune system is re-targeted/reactivated to cause

By getting access to the tumor and normal whole-genome sequencing data from high- and low-grade pediatric glioma patients, as well as the patient-matched clinical data, Eigengene proposes to create personalized diagnostic and prognostic tests for pediatric gliomas. Eigengene develops powerful uni

Immunotherapy holds great promise in the treatment of pediatric central nervous system tumors. This is especially true in high grade tumor pathologies (high grade glioma, DIPG, ATRT, medulloblastoma, etc.) where the underlying biology does not seem to involve targetable driver mutations, but rath

The goal of this project is to do an analysis of the spatial evolution and genetic-epigenetic landscape in Gliomatosis Cerebri and other HGG. To do this, the team will use innovative tools in computational biology to map the spatial differences in glioma progression.

The team, lead by Dr. Vaske is generating mutational, transcriptional, and integrative profiles of individual tumors. Integrative profiles will summarize mutation and expression features at the pathway level, or by other groupings. They also are comparing the profiles of CBTN samples to each othe

In this study, Dr. Diskin and her team are performing a primary analysis of recently-generated whole genome sequencing (WGS) and matched RNA-sequencing. This study will take advantage of the various cancer types sequenced to identify pleotropic and histotypes-specific alterations, somatic drivers

This project will analyse the pediatric brain tumor RNAseq data for fusions. A small cohort of the same tumors at Weill Cornell will be compared to the Pediatric Brain Tumor Atlas.

This project aims to identify cooperating mutations with NF1 in Neurofibromatosis type I patients with brain tumors. This project will result in a comprehensive list of genes that are co-mutated with NF1.

Ependymomas constitute nearly one third of the CNS neoplasms among children aged < 3 years. The disease remains a significant therapeutic challenge, with a 5-year overall survival rate < 55 % among this age group and no available chemotherapy of proven efficacy. The breadth of therapies is

This research will evaluate associations between the presence or absence of various polymorphisms from brain tumor biospecimens and neuropsychological functioning. The study will include measures of cognitive, emotional, social and behavioral functioning through the use of direct assessment, self

The Treehouse Childhood Cancer Initiative research focuses on the value of tumor gene expression analysis using RNA sequencing for detecting aberrations in the genome and epigenome. The main objective of this project is to identify therapeutically actionable oncogenes with outlier expression in a

Many brain tumor patients at our institution have clinical sequencing of their tumors in addition to having tissue sent to the Children's Brain Tumor Network (CBTN) and included in the whole bank sequencing project. We want to compare the genetic results of our clinical NGS performed on the

Mixed Neuronal-Glial Tumors (MNGT) are a benign category of tumors associated with seizures presenting in children and young adults. The genomic landscape of these tumors is an area of active research, and correlation with histologic tumor subtypes is in flux. Through clinical ascertainment, we h

Pediatric brain tumors are the leading cause of disease related death in children. Major factors contributing to treatment failures for children with brain tumors include: i) the lack of comprehensive molecular description of the disease and an associated dearth of integration of the tumors’ biol

The goal of this study is to determine the overall layout of infiltrating immune repertoire in pediatric solid tumors. We will perform immune repertoire analysis and deconvolute immune components from RNA-seq data using transcript counts to infer the fraction of ~20 immune cell types infiltrating

We aim to screen the established CBTN database of pediatric brain tumor tissue to identify a list of proteins. We then aim to use an established protocol to compare this list to normal tissue expression lists, to potentially compile a list of proteins expressed in pediatric brain tumors.

We aim to investigate the role of genetic interactions and their contribution to different pediatric cancers. In particular, we focus on cooperative and mutually exclusive interactions between genes, pathways and processes altered in pediatric cancers as exhibited in cancer genomes of patients.

Embryonal tumor with multilayer rosettes (ETMR) is a rare and highly-aggressive CNS neoplasm which occurs almost exclusively in young children and is associated with an extremely poor prognosis. Due the tumor’s rarity, with less than 300 cases reported in the literature, the classification of thi

Meningiomas, neoplasms of mesodermal-arachnoid origin, are the most common primary intracranial and spinal tumors. About 80% of them show benign features and are amenable to surgical resection alone. 20%, however, require extensive multimodal treatment (repeat surgery, radiotherapy, or systemic c

Exome sequencing (ES) is the most advanced standard-of-care genetic test for children with multiple congenital anomalies. Yet, the diagnostic rate of ES is only 31%1–3. One challenge is that each test generates hundreds of thousands of variants that must be prioritized via a computational pipelin

This pilot project at Lurie Children's Hospital will catalog germline genomic alterations in the CBTN database (SNVs, CNVs, Indels, etc.) and see if any genetic alterations are enriched in the radiation injury group (patients that developed radiation necrosis).

We have recently established the landscape of germline mitochondrial DNA (mtDNA) variants and somatic mtDNA mutations in pediatric malignancies, from mining the paired tumor-normal whole-genome sequencing data of over 600 pediatric cancer patients of 23 subtypes. A main finding of the study is th

Major advances have been achieved in the discovery and application of targeted therapy for adult solid tumors. Nevertheless, therapeutic options for pediatric solid tumors have been limited. Current precision medicine programs focus on genomic sequencing to identify discrete mutations that may pr

Brain tumors are the leading cause of cancer related death in children. While significant advances have been made in molecularly subgrouping tumors of same pathological diagnosis, little is known about the differences of tumor biology and the clinical outcomes among racial/ethnic populations. By

Ependymoma is a heterogeneous disease comprising at least nine distinct molecular groups. The most frequent and most aggressive groups of ependymoma are the RELA and PFA groups that predominantly occur in children. Although in recent years we and others identified the main drivers of these groups

Medulloblastoma is the most prevalent and aggressive brain tumor in the pediatric population. We have to better understand the mechanisms of tumor formation in all subtypes of medulloblastoma so as to use that knowledge to devise new therapies that will be more efficient and also less toxic than

Ependymoma is the third most common brain tumor of childhood, and current treatments are limited to surgery and radiation even in very young children. Both supratentorial and posterior fossa ependymoma are relatively chemotherapy resistant, and patients with relapsed or subtotally resected diseas

Primary resistance to chemotherapy is a major challenge in treating brain tumors today. Finding novel and specific tumor dependencies is therefore essential for effective drug development and improving patient outcomes.High-grade gliomas (HGG) are the most aggressive brain tumors in childr

Oligodendrogliomas are primary brain tumors with oligodendrocytic features that arise in adults and children. Although these cancers are relatively indolent in comparison to other primary brain tumors, they tend to occur in younger people and are difficult to treat, resulting in devastating loss

Glioblastoma is the most aggressive brain tumor in adults and children and is typically fatal despite multimodality therapy. The two year overall survival rate of less than 30% in newly diagnosed patients has not improved in over a decade. Treatment options for malignant gliomas are significantly

Pediatric Low Grade Gliomas (PLGG) are the most common brain tumor in children. BRAFV600E is found in up to 20% of PLGG cases and is associated to a worse prognosis with a 75% risk of relapse and progression. Relapse, progression and Malignant transformation (MT) into secondary High Grade Glioma

Brain tumors are rare and when combined with other nervous system tumors account for ~ 2% of all cancers; however, they are the second most common type of pediatric cancer and the leading cause of childhood cancer-related mortality. The etiology and molecular features of most pediatric brain tumo

Brain cancer has become the leading cause of death in children with cancer. Brain tumor research generated little advances that have translated into meaningful clinical benefit for pediatric patients. One of the main reasons which significantly slowed down the progress of the scientific developme

Choroid plexus tumors (CPT) are rare intraventricular neuroectodermal lethal neoplasms. Around 80% of choroid plexus carcinoma (CPC) arise in children, in whom they constitute 15–20% of CPT. Clinically, this group of tumors tends to cause hydrocephalus and increased intracranial pressure. Surgica

Irrespective of entity, patients who relapse from cancer have an extremely dismal outlook, with nearly all patients succumbing to their recurrent disease. This is particularly true for patients with medulloblastoma (MB), the most common malignant brain tumor in children, where tumor relapse is am

We have previously reported a high frequency of AKT activation, a downstream target of PTEN, in pediatric high-grade gliomas (pHGGs), as assessed by immunohistochemistry (IHC), and demonstrated that this was associated with an adverse prognosis. Compared to adult high-grade gliomas, pHGGs show a

Childhood thalamic tumors are relatively rare cancers, accounting for 5% of all pediatric brain tumors. These tumors are usually of glial origin and thalamic lesions are histologically classified as either low grade gliomas (LGG) or high grade gliomas (HGG) according to the World Health Organizat

The CBTN was presented with a unique opportunity to sequence a large portion, approximately 1650 aliquots, of our biospecimens by NantOmics.

DNA replication in cancer cells is often accompanied by stalling and collapse of the replication fork, providing a therapeutic vulnerability if unable to be repaired. Endogenous replication stress occurs when the replication fork stalls, but the MCM helicase continues to unwind downstream causing

Low grade gliomas (LGG) develop in ~20% of children with NF1, occurring most commonly within the optic pathway (optic pathway glioma; OPG). While the majority of these tumors are indolent pilocytic astrocytomas (Pas) which do no necessitate medical intervention, 30-50% of the NF1-OPGs cause visua

We will apply different algorithms to measure research use statement telomere DNA abundance from sequencing data across tumors.We will study the association between tumor mutational background and telomere abundance

There is increasing evidence that a significant proportion of children with Central Nervous System (CNS) cancers harbor underlying cancer predisposing germline mutations. For example, in a large study of pediatric cancer (Grobner et al and Ma et al, Nature 2018), approximately 8% of

To identify novel therapeutic targets of pediatric, we conducted an unbiased meta-analysis of gene signatures from multiple public datasets including the Cancer Genome Atlas (TCGA) Low-grade Glioblastoma. Our preliminary work identified a gene network centered on the FoxM1 transcription factor. F

Brain tumors are the most common pediatric solid tumor, affecting 1-5 per 100,000 children. While advancements in cancer therapies have led to an improved survival rate in certain brain cancers, many brain tumor types are poorly understood and lack effective treatment options. Certain subtypes of

Meningiomas are a common central nervous system (CNS) tumor that arise from arachnoidal cells of the meninges that cover and protect the brain and spinal cord. The World Health Organization (WHO) classification strategy defines meningiomas into three pathologically distinct groups based on morpho

Brain tumors are the most common cause of pediatric cancer-related death in the United States. Glial tumors (astrocytomas, oligodendrogliomas, etc.) are the most common class of pediatric brain tumors with diffuse astrocytomas being of particular interest because they infiltrate normal brain tiss

The pediatric brain tumor dataset will be used for training, validating, and testing the transfer learning approach for increased performance in the classification and segmentation tasks. Even with the problem of structural and tissue differences from child and adult brains, we will attempt the u

Structural variations (SVs) are large scale changes of DNA typically affecting more nucleotides than other forms of genetic variants. We aim to study how somatic SVs are formed, how they drive disease progression and how they impact treatment in pediatric brain tumors.

Diffuse intrinsic pontine glioma (DIPG) is the leading cause of death in children with brain cancers and is considered to be uniformly fatal with median overall survival of only 8-11 months. Radiation is the only therapy proven to increase survival and that by meager 3-6 months. These tumors cann

We previously developed rMATS, a robust statistical framework designed for quantifying alternative splicing and identifying differential splicing events in RNA-seq data from many biological samples (Shen et al., PNAS, 2014, 111(51): E5593–E5601). Since its release, the rMATS software has received

My institution serves as reference neuropathology center for the international choroid plexus tumor registry (CPT-SIOP, International Society of Pediatric Oncology) and we thus frequently encounter CPT tissue samples. Previously, we have shown that methylation profiling of CPT reveals three clini

Diffuse intrinsic pontine glioma (DIPG) is an aggressive type of brainstem cancer that targets young children. Complete resection is not possible, and chemotherapy and radiotherapy are currently only palliative. Prognosis is dismal. Novel approaches are urgently needed to treat this disease.

We wish to analyze genetic sequences of samples of different families of pediatric brain tumors, and thereafter perform machine learning-based natural language processing algorithms on text-based clinical data from the same specimens.

We are currently generating various models of malignant childhood brain tumors in mice. We mainly focus on medulloblastoma but are also studying malignant glioma, DIPGs and choroid plexus carcinomas. Our focus is on the signaling pathways of MYC and MYCN cancer genes that are commonly dysregulate

Microsatellites consist of a 1-6 base pair unit repeated in tandem to form an array. Over 600,000 unique microsatellites exist in the human genome, and are often embedded in gene introns, exons, and regulatory regions. Interestingly, the length of microsatellite loci frequently change due to stra

Anaplastic pleomorphic xanthoastrocytomas (PXAs) account for less than 1% of all brain tumors. Anaplastic PXAs can be diagnosed de novo or at the time of progression from lower grade tumors. The rate of malignant transformation of grade II to grade III PXAs is between 10% and 25%. The prog

Neurofibromatosis type 1 (NF-1) is the most common cancer predisposition syndrome associated with central nervous system (CNS) cancers. Although other non-NF-1 RASopathies, including Noonan syndrome are as prevalent a NF-1, their association with CNS cancers has been uncommonly reported. The phen

The objective of this project is to examine the trajectories of height, weight, and body mass index (BMI) in individuals in the CBTN with pathological diagnoses of craniopharyngioma. Our overarching research goal is to develop a risk prediction model for the development of hypothalamic obesity re

Outcomes in pediatric cancer have steadily improved over the last several decades. As a direct result, there is increased focus on decreasing the long-term side effects of treatment. One emerging field to address this issue is “Pharmacogenomics”, using genotype to predict an individual’s response

Early analyses by our group and others have suggested that semi-quantitative radiographic (radiomic) features prior to and following therapy may aid disease classification at diagnosis, prognostication, and improve our ability to distinguish between challenging imaging phenotypes following therap

Cellular immunity mediated by T-cells is responsible for the detection and neutralization of pathogenic threats. T-cell receptors (TCRs) are highly specialized extracellular receptors that are essential to T-cell specificity and can characterize the T-cell immune status in patients, and normal in

The stem cell-like phenotype of various cancer type is directly correlated with increased malignancy as well as with resistance to conventional and targeted therapies. Number of tumour type and subtypes can be distinguished by various features of plutipotency. It is also postulated and supported

We hypothesize that macrophages within pediatric brain tumors (PBT) may enable local tumor regrowth and spinal metastasis. To determine the burden of infiltrating macrophage in human PBT tissue samples, we plan to correlate gene expression of macrophage signature genes with patterns of clinical p

The proposed study will be an exploratory examination of fusions and expression in pediatric tumors including neuroblastoma, low and high grade glioblastoma, medulloblastoma, choroid plexus carcinoma, ependymoma and other rare diagnoses. St. Jude has RNA seq from approximately 1200 brain tumor pa

By integrative analysis of somatic structural variants (SSVs)  and gene expression data from the ~854 pediatric brain cancers in the Children's Brain Tumor Tissue Consortium (CBTTC), we will identify genes for which the nearby presence (within 1 Mb) of a somatic SSV breakpoint is associated

This project aims at identifying variants in the CBTN germline DNA whole genome sequencing data that are reported and/or found in other diseases, esp. birth defects and rare Mendelian disorders, hoping to explain/reveal shared genetics between pediatric cancer and rare diseases.

Many patients who have both familial and sporadic forms of cerebral cavernous malformations (CCMs) have mutations in genes that are also known to play a role in cancer genesis. Some of these genes either play a role in oncogenesis, anti-apoptosis, or angiogenesis. Many pediatric patients with tum

Proteogenomics, a field presently dealing primarily with the tailoring of individualized protein sequence databases, via utilization of various sources of genetic sequencing and expression information, for optimal success in mass spectrometry-based protein discovery and quantification. Such metho

Standard histopathological evaluation is no longer considered the end-point for patients' treatment decision. Genetic and molecular evaluation has shown that tumors with the same histopathological features can behave differently clinically. Some recent studies have found that imaging signatu

Paediatric cancer is a rare disease. This makes it challenging or impossible to recruit large cohorts of paediatric cancer cases and limits our understanding of the biology and optimal treatment of childhood cancer. To resolve this we must share data across international paediatric cancer cohorts

Precision oncology relies on the identification of targetable driver mutations. However, based on our current coding-focused understanding of the cancer genome, many paediatric cancers seem to lack driver mutations entirely. We hypothesise that the apparent low rate of driver mutations in some pa

We have developed an algorithm to detect DNA damage in the blood using 30x-depth WGS. This yields a quantitative biomarker of DNA damage susceptibility, which we have shown prospectively in adults to be strongly associated with a future cancer diagnosis. Here we will investigate whether this biom

Children with high-grade glioma, diffuse intrinsic pontine glioma, rhabdoid brain tumors, and certain other types of brain tumors experience a low likelihood of survival even with maximal therapy, including surgery, intensive chemotherapy, and radiation therapy.

DIPGs are especially lethal and confer a despairingly short 11-month median survival due to their aggressive phenotype and lack of therapeutic options. Molecular characterization of pediatric brain tumors is stimulating the development and testing of targeted therapies for precision medicine. How

Cancer is a leading cause of death for children and adolescents worldwide. Brain tumors are among the most common childhood cancers and one of the most difficult to treat (WHO fact sheet 2018). Neoantigens are the future of personalized cancer vaccines and expected to be key markers for predictio

This project will investigate the role of mutations in mitochondrial DNA with brain cancer progression/aggressiveness.

Objective of the proposed research is to advance the field of unsupervised visual anomaly detection (UAD), with a focus on medical imagery. Developed UAD methods will be evaluated on all the available medical imagery available as part of the Pediatric Brain Tumor Atlas, where anomaly detection (e

Our focus is on ependymoma, a pediatric brain tumor, for which still today subgroups exist where no clear drivers or drug targets have been identified. However, we would like to consider our results also in the context of other brain tumors.

Cancer is the major cause of childhood mortality worldwide. The cancer incidence rate is approximately 150 cases per million children in the U.S. of which leukemia followed by central nervous system tumors are the most common malignancies. Despite the improvements in treatment of childhood cancer

Our research seeks to uncover more about why adult and paediatric chordoma by studying the geneticpatterns.

We are part of the EU funded project “individualized paediatric cure- iPC” (https://ipc-project.eu/) that aims to find novel therapeutic routes for children with cancer based on systems biological analysis and modeling of large scale genomic, transcriptomic and proteomic data sets. High grade gli

Our goal is to integrate mouse and human multi-omics data to identify oncogenic events in pediatric brain tumors. In our recent study (Wang et al. Nat. Comm. 2019), we profiled transcriptome, whole proteome and phosphoproteome in two glioma mouse models driven by mutated RTK oncogenes, PDGFRA and

Central nervous system tumors are leading cause of fatality among children. Current therapeutic approaches focusing primarily on surgical resections and chemotherapy, in even in cases of successful treatment, results in lower standard of life arising from treatment associated cognitive and behavi

The major histocompatibility complex (MHC) has been documented to be involved in a variety of immunological processes; however, it often eludes understanding because of the complexity of the region due to factors like strong linkage disequilibrium (LD) and highly polymorphic loci.The probl

We have previously performed a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer (Groebner et al., Nature 2018 https://www.ncbi.nlm.nih.gov/pubmed/29489754). Usi

The proposed research study will attempt to create a larger, retrospective review of patients with CNS tumors and BCOR mutations. We hope to learn more about how tumors with BCOR mutations behave and understand more about the differences in tumor types and outcomes including PFS and OS.

This collaborative project by CBTN and Parker Institute (PICI) investigators aims to examine the immune and tumor microenvironment in situ in pediatric brain tumor tissues, particularly in response to immunotherapy. Integration of single cell multiplex imaging of tissue microarray targets (TMAs)

We have generated preliminary data showing that retroviral elements actively transpose throughout the process of tumor growth and relapse in pediatric HGGs. We hypothesize that transposable elements have a crucial role in contributing to clonal and subclonal genomic evolution in this cancer.

Normal human development, disease risk, and response to treatments are often different in males and females. Cancer is no exception, and we are working to determine whether cancer treatments should be optimized independently for males and females. The analysis of the CBTN's Pediatric Brain T

It is currently unknown to what extent protein expression is under genetic control in pediatric brain cancers. Here, we aim to identify cis-acting mechanisms that affect protein expression levels and map trans-acting germline variants that perturb proteinprotein interactions within individual bra

We intend to develop a set of tools which will use artificial intelligence (AI) to aid with the clinical management of pediatric brain tumors. These tools will automatically detect brain tumors in MRI scans, and provide predictions as to what subtype of tumor the patient has. We will also use AI

Intracranial germ cell tumor is a very dangerous pediatric cancer but lacking sufficient study. Although previous research have revealed some key mechanism (KIT/AKT & RAS/MAPK pathway mutation) of this cancer, there are still a lot of cases can not be covered by current exist theory. In this

The objective of this project is to investigate whether aberrant splicing candidates resulting from transcriptome-wide dysregulation of alternative splicing in high grade gliomas (HGGs) could be a source for novel neoantigen expression in tumors, that are distinct from missense mutations.

The comparative genomics of spontaneous tumors across species provides a unique advantage to identify variants in shared and evolutionarily constrained regions in cancer genome that are occurred by selecting cells that carry favorable mutations in somatic evolution of cancers. Our group has been

DIPG remains a fatal disease and new treatment approaches are necessary. A novel Cancer Systems Biology approach identifies master regulator (MR) proteins that are necessary for tumor growth and predicts and prioritizes drugs that reverse their effects. This study will apply such an approach to e

Diffuse intrinsic pontine glioma (DIPG) is a rare childhood brain cancer that is fatal in over 99% of all cases. We believe that ion channels, pore-forming proteins that move chemicals like calcium and potassium in and out of cells, have a role in drug resistance. WE will use this data to determi