Gnana Prakash Balasubramanian
A5032603745- FOXO transcription factor regulation
- Childhood Cancer Survivors' Quality of Life
- Radiation Therapy and Dosimetry
- Renal and related cancers
- Ferroptosis and cancer prognosis
- Testicular diseases and treatments
- Glioma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Neuroblastoma Research and Treatments
- CNS Lymphoma Diagnosis and Treatment
- Genetic factors in colorectal cancer
- Pancreatic and Hepatic Oncology Research
- Acute Lymphoblastic Leukemia research
- Epigenetics and DNA Methylation
- CAR-T cell therapy research
- DNA Repair Mechanisms
- Cancer Immunotherapy and Biomarkers
- Lymphoma Diagnosis and Treatment
- Lung Cancer Research Studies
- BRCA gene mutations in cancer
- Sarcoma Diagnosis and Treatment
- PARP inhibition in cancer therapy
- RNA modifications and cancer
- Brain Metastases and Treatment
- Genomics and Rare Diseases
German Cancer Research Center
2015-2024
Heidelberg University
2015-2024
Deutschen Konsortium für Translationale Krebsforschung
2016-2024
Hopp Children's Cancer Center Heidelberg
2018-2024
National Center for Tumor Diseases
2016-2024
University Hospital Heidelberg
2017-2024
Sabin Vaccine Institute
2023
University of Cincinnati
2023
Dana-Farber Cancer Institute
2023
DKFZ-ZMBH Alliance
2017
Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into biology. Here we present comprehensive analysis of genetic alterations in pan-cancer cohort including 961 tumours from children, adolescents, young adults, comprising 24 distinct molecular cancer. Using standardized workflow, identified marked terms mutation frequency significantly mutated genes comparison previously analysed adult cancers....
Abstract INFORM is a prospective, multinational registry gathering clinical and molecular data of relapsed, progressive, or high-risk pediatric patients with cancer. This report describes long-term follow-up 519 in whom alterations were evaluated according to predefined seven-scale target prioritization algorithm. Mean turnaround time from sample receipt was 25.4 days. The highest priority level observed 42 (8.1%). Of these, 20 received matched targeted treatment median progression-free...
Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell (DLBCLs) confined to (CNS). Molecular drivers PCNSL have not been fully elucidated. Here, we profile and compare whole-genome transcriptome landscape 51 CNS (CNSL) 39 follicular lymphoma 36 DLBCL cases outside CNS. We find recurrent mutations in JAK-STAT, NFkB, receptor signaling pathways, including hallmark MYD88 L265P (67%) CD79B (63%), CDKN2A deletions (83%). PCNSLs exhibit significantly more focal...
Incomplete understanding of the metastatic process hinders personalized therapy. Here we report most comprehensive whole-genome study colorectal metastases vs. matched primary tumors. 65% somatic mutations originate from a common progenitor, with 15% being tumor- and 19% metastasis-specific, implicating higher mutation rate in metastases. Tumor- metastasis-specific harbor elevated levels BRCAness. We confirm multistage progression new components ARHGEF7/ARHGEF33. Recurrently mutated...
iTHER is a Dutch prospective national precision oncology program aiming to define tumour molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory paediatric tumours. Between April 2017 2021, 302 samples from 253 patients were included. Comprehensive profiling including low-coverage whole genome sequencing (lcWGS), exome (WES), RNA (RNA-seq), Affymetrix, and/or 850k methylation was successfully performed for 226 at least 20% content. Germline...
Abstract Long-term complications such as radiation-induced second malignancies occur in a subset of patients following radiation-therapy, particularly relevant pediatric due to the long follow-up period case survival. Radiation-induced gliomas (RIGs) have been reported after treatment with cranial irradiation for various primary acute lymphoblastic leukemia (ALL) and medulloblastoma (MB). We perform comprehensive (epi-) genetic expression profiling RIGs arising MB (n = 23) ALL 9). Our study...
Abstract Thrombospondins (TSPs) are multidomain glycoproteins with complex matricellular functions in tissue homeostasis and remodeling. We describe a novel role of TSP as Wnt signaling target the basal eumetazoan Hydra . Proteome analysis identified magnipapillata (HmTSP) major component cnidarian mesoglea. In general, domain organization TSPs is related to pentameric bilaterians, phylogenetic analyses formed separate clade high sequence diversity. HmTSP expression polyps was restricted...
O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status is a predictive biomarker in glioblastoma patients. Glioblastoma without hypermethylated MGMT largely resistant to treatment with temozolomide. These patients are particular need of new approaches, which offered by biomarker-driven clinical trials targeted drugs based on molecular characterization individual tumors.In preparation for an upcoming study, comprehensive profiling approach was undertaken tissues from 43...
Abstract Background Pediatric patients with relapsed or refractory disease represent a population desperate medical need. The aim of the INFORM (INdividualized Therapy FOr Relapsed Malignancies in Childhood) program is to translate next generation molecular diagnostics into biomarker driven treatment strategy. consists two major foundations: registry providing screening platform and INFORM2 series phase I/II trials. NivEnt trial aims determine recommended 2 dose (RP2D) combination nivolumab...
A hierarchically organized cell compartment drives colorectal cancer (CRC) progression. Genetic barcoding allows monitoring of the clonal output tumorigenic cells without prospective isolation. In this study, we asked whether tumor clone-initiating (TcICs) were genetically heterogeneous and differences in self-renewal activation reflected differential kinetics among individual subclones or functional hierarchies within subclones. Monitoring genomic subclone three patient tumors corresponding...
Abstract Forkhead box R2 (FOXR2) is a forkhead transcription factor located on the X chromosome whose expression normally restricted to testis. In this study, we performed pan-cancer analysis of FOXR2 activation across more than 10,000 adult and pediatric cancer samples found be aberrantly upregulated in 70% all types 8% individual tumors. The majority tumors (78%) expressed through previously undescribed epigenetic mechanism that involves hypomethylation novel promoter, which was...
LBA10503 Background: Several pediatric precision oncology programs have identified molecular actionable variants. However, the clinical benefit is largely unknown. We here report a target prioritization algorithm and associated outcome. Methods: INFORM prospective, non-interventional, multi-center, multi-national, feasibility registry collecting data. Patients with refractory/relapsed/progressive malignant disease, including primary diagnosis high-risk entities, can be enrolled. Fresh frozen...
TPS10065 Background: Immune checkpoint inhibition in children has shown limited success rates until now. This is most likely due to the fact that vast majority of pediatric cancers are so-called immunologic cold tumors, and patients have been enrolled an unselected manner single agent trials. Recently, it class I selective HDAC inhibitor entinostat significant immune enhancing activity vitro vivo. mediated through multiple mechanisms including depletion myeloid-derived suppressor cells,...
Abstract Inactivating alterations of tumor suppressor gene TP53 are a hallmark progression in various cancer entities. Unfortunately, inactivation has not yet provided an actionable vulnerability. To investigate distribution, mutational pattern and impact pediatric high-grade gliomas (pedHGG), we investigated 407 pedHGG by analyzing genomic sequencing survival data collected through the INFORM MNP molecular diagnostic pipelines. Nearly half (47%) showed signs inactivation. A second hit...
High-grade glioma (HGG) of the spinal cord constitutes rare tumors in pediatric population. Knowledge molecular profile this HGG (pedHGG) subgroup is limited and clinical outcome poor. Therefore, aim study to provide more profound investigations characteristics features these tumors. Between January 2015 October 2023, 17 with histology were analyzed by Individualized Therapy For Relapsed Malignancies Childhood (INFORM) precision oncology registry. Comprehensive profiling (including...
Abstract Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell (DLBCLs) confined to (CNS). Despite extensive research, molecular alterations leading PCNSL have not been fully elucidated. In order provide a comprehensive description genomic and transcriptional landscape PCNSL, we here performed whole-genome transcriptome sequencing integrative analysis 51 presenting in CNS, including 42 EBV-negative 6 secondary CNS (SCNSL) 3 EBV+ CNSL matched controls. The...
10509 Background: Relapses from high-risk tumors pose a major clinical challenge in pediatric oncology. The German INFORM registry (INdividualized therapy FOr Relapsed Malignancies children) addresses this problem using integrated next-generation sequencing to rapidly identify patient-specific therapeutic targets. Methods: Whole-exome, low-coverage whole-genome and RNA is complemented with microarray-based DNA methylation profiling. Identified alterations are discussed prioritized according...