GENE-07. LIQUID BIOPSY DETECTION OF GENOMIC ALTERATIONS IN PEDIATRIC BRAIN TUMORS FROM CELL-FREE DNA IN PERIPHERAL BLOOD, CSF, AND URINE

Tumors of the central nervous system are the most frequent solid tumor type and the major cause for cancer-related mortality in children and adolescents. These tumors are biologically highly heterogeneous and comprise various different entities. Molecular diagnostics are already well-established for pediatric brain tumors and have facilitated a more accurate patient stratification. The availability of targeted, biomarker-driven therapies has increased the necessity of longitudinal monitoring of molecular alterations within tumors for precision medicine-guided therapy. Nevertheless, diagnosis is still primarily based on analyses of the primary tumor and follow-up is usually performed by imaging techniques which lack important information on tumor biology possibly changing the course of the disease. To overcome this shortage of longitudinal information, liquid biopsy has emerged as a promising diagnostic tool representing a less-invasive source of biomarkers for tumor monitoring and therapeutic decision making. Novel ultrasensitive methods for detection of allele variants, genetic alterations with low abundance, have been developed and are promising tools for establishing and integrating liquid biopsy techniques into clinical routine. Pediatric brain tumors harbor multiple molecular alterations with the potential to be used as liquid biomarkers. Consequently, studies have already investigated different types of biomarker in diverse entities of pediatric brain tumors. However, there are still certain pitfalls until liquid biomarkers can be unleashed and implemented into routine clinical care. Within this review, we summarize current knowledge on liquid biopsy markers and technologies in pediatric brain tumors, their advantages and drawbacks, as well as future potential biomarkers and perspectives with respect to clinical implementation in patient care.

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GENE-09. PRECISION MEDICINE ANALYSIS OF 203 PEDIATRIC BRAIN TUMORS REVEALS CLINICALLY RELEVANT GENOMIC ALTERATIONS

Neuro-Oncology ◽

10.1093/neuonc/nox083.080 ◽

2017 ◽

Vol 19 (suppl_4) ◽

pp. iv20-iv20 ◽

Cited By ~ 1

Author(s):

Pratiti Bandopadhayay ◽

Shakti Ramkissoon ◽

Jaeho Hwang ◽

Lori Ramkissoon ◽

Noah Greenwald ◽

...

Keyword(s):

Brain Tumors ◽

Precision Medicine ◽

Pediatric Brain Tumors ◽

Genomic Alterations ◽

Medicine Analysis ◽

Pediatric Brain

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Treatment approaches combining cytostatic drugs with the oncolytic parvovirus H-1 increase cytotoxic effects in cell culture models of highly malignant pediatric brain tumors

Klinische Pädiatrie ◽

10.1055/s-0034-1393947 ◽

2014 ◽

Vol 226 (06) ◽

Author(s):

C Westphal ◽

S Öztürk ◽

R Josupeit ◽

B Leuchs ◽

O Witt ◽

...

Keyword(s):

Cell Culture ◽

Brain Tumors ◽

Pediatric Brain Tumors ◽

Cytostatic Drugs ◽

Cytotoxic Effects ◽

Treatment Approaches ◽

Culture Models ◽

Pediatric Brain ◽

Cell Culture Models

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Pediatric Brain Tumors: Genomics and Epigenomics Pave the Way

Critical Reviews™ in Oncogenesis ◽

10.1615/critrevoncog.2015013565 ◽

2015 ◽

Vol 20 (3-4) ◽

pp. 271-299 ◽

Cited By ~ 4

Author(s):

Adam M. Fontebasso ◽

Nada Jabado

Keyword(s):

Brain Tumors ◽

Pediatric Brain Tumors ◽

Pediatric Brain ◽

The Way

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Cell free DNA as an evolving liquid biopsy biomarker for initial diagnosis and therapeutic nursing in Cancer- An evolving aspect in Medical Biotechnology

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666201211102710 ◽

2020 ◽

Vol 21 ◽

Author(s):

Suman Kumar Ray ◽

Sukhes Mukherjee

Keyword(s):

Tumor Cells ◽

Liquid Biopsy ◽

Cancer Metastasis ◽

Nuclear Dna ◽

Fragment Size ◽

Body Fluids ◽

Response To Therapy ◽

Significant Information ◽

Cell Free Dna ◽

Free Dna

: Cell-free DNA (cfDNA) is present in numerous body fluids in addition to initiates generally from blood cells. It is undoubtedly the utmost promising tool among all components of liquid biopsy. Liquid biopsy is a specialized method investigating the nonsolid biological tissue by revealing of circulating cells, cell free DNA etc. that enter body fluids. Since, cancer cells disengage from compact tumors circulate in peripheral blood, evaluating blood of cancer patients holds the opportunities for capture and molecular level analysis of various tumor-derived constituents. Cell free DNA samples can deliver a significant perceptions into oncology, for instance tumor heterogeneity, instantaneous tumor development, response to therapy and treatment, comprising immunotherapy and mechanisms of cancer metastasis. Malignant growth at any phase can outhouse tumor cells in addition to fragments of neoplasticity causing DNA into circulatory system giving noble sign of mutation in the tumor at sampling time. Liquid biopsy distinguishes diverse blood based evolving biomarkers comprising circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) or cfDNA, circulating RNA (cfRNA) and exosomes. Cell free DNA are little DNA fragments found circulating in plasma or serum, just as other fluids present in our body. Cell free DNA involves primarily double stranded nuclear DNA and mitochondrial DNA, present both on a surface level and in the lumen of vesicles. The probable origins of the tumor-inferred portion of cfDNA are apoptosis or tumor necrosis, lysis of CTCs or release of DNA from the tumor cells into circulation. The evolution of innovations, refinement and improvement in therapeutics for determination of cfDNA fragment size and its distribution provide significant information related with pathological conditions of the cell, thus emerging as promising indicator for clinical output in medical biotechnology.

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Corrigendum to “Impact of SCID mouse gender on tumorigenicity, xenograft growth and drug-response in a large panel of orthotopic PDX models of pediatric brain tumors” [Cancer Lett. 493 (2020) 197–206]

Cancer Letters ◽

10.1016/j.canlet.2020.12.007 ◽

2020 ◽

Author(s):

Lin Qi ◽

Mari Kogiso ◽

Yuchen Du ◽

Huiyuan Zhang ◽

Frank K. Braun ◽

...

Keyword(s):

Brain Tumors ◽

Scid Mouse ◽

Drug Response ◽

Pediatric Brain Tumors ◽

Xenograft Growth ◽

Large Panel ◽

Pediatric Brain ◽

Pdx Models

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A pediatric brain tumor atlas of genes deregulated by somatic genomic rearrangement

Nature Communications ◽

10.1038/s41467-021-21081-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yiqun Zhang ◽

Fengju Chen ◽

Lawrence A. Donehower ◽

Michael E. Scheurer ◽

Chad J. Creighton

Keyword(s):

Brain Tumor ◽

Brain Tumors ◽

Tyrosine Kinases ◽

Pediatric Brain Tumor ◽

Pediatric Brain Tumors ◽

Altered Expression ◽

Critical Pathways ◽

Cis Regulation ◽

Or Gene ◽

Pediatric Brain

AbstractThe global impact of somatic structural variants (SSVs) on gene expression in pediatric brain tumors has not been thoroughly characterised. Here, using whole-genome and RNA sequencing from 854 tumors of more than 30 different types from the Children’s Brain Tumor Tissue Consortium, we report the altered expression of hundreds of genes in association with the presence of nearby SSV breakpoints. SSV-mediated expression changes involve gene fusions, altered cis-regulation, or gene disruption. SSVs considerably extend the numbers of patients with tumors somatically altered for critical pathways, including receptor tyrosine kinases (KRAS, MET, EGFR, NF1), Rb pathway (CDK4), TERT, MYC family (MYC, MYCN, MYB), and HIPPO (NF2). Compared to initial tumors, progressive or recurrent tumors involve a distinct set of SSV-gene associations. High overall SSV burden associates with TP53 mutations, histone H3.3 gene H3F3C mutations, and the transcription of DNA damage response genes. Compared to adult cancers, pediatric brain tumors would involve a different set of genes with SSV-altered cis-regulation. Our comprehensive and pan-histology genomic analyses reveal SSVs to play a major role in shaping the transcriptome of pediatric brain tumors.

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RONC-19. TWO CASES OF RE-IRRADIATION FOR LATE RECURRENT OR RADIATION-INDUCED TUMOR AFTER RADIATION THERAPY FOR PEDIATRIC BRAIN TUMORS

Neuro-Oncology ◽

10.1093/neuonc/noaa222.788 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii459-iii459

Author(s):

Takashi Mori ◽

Shigeru Yamaguchi ◽

Rikiya Onimaru ◽

Takayuki Hashimoto ◽

Hidefumi Aoyama

Keyword(s):

Radiation Therapy ◽

Brain Tumors ◽

Tumor Resection ◽

Intensity Modulated Radiation Therapy ◽

Late Recurrence ◽

Pediatric Brain Tumors ◽

Suprasellar Region ◽

Radiation Induced ◽

Pediatric Brain

Abstract BACKGROUND As the outcome of pediatric brain tumors improves, late recurrence and radiation-induced tumor cases are more likely to occur, and the number of cases requiring re-irradiation is expected to increase. Here we report two cases performed intracranial re-irradiation after radiotherapy for pediatric brain tumors. CASE 1: 21-year-old male. He was diagnosed with craniopharyngioma at eight years old and underwent a tumor resection. At 10 years old, the local recurrence of suprasellar region was treated with 50.4 Gy/28 fr of stereotactic radiotherapy (SRT). After that, other recurrent lesions appeared in the left cerebellopontine angle, and he received surgery three times. The tumor was gross totally resected and re-irradiation with 40 Gy/20 fr of SRT was performed. We have found no recurrence or late effects during the one year follow-up. CASE 2: 15-year-old female. At three years old, she received 18 Gy/10 fr of craniospinal irradiation and 36 Gy/20 fr of boost to the posterior fossa as postoperative irradiation for anaplastic ependymoma and cured. However, a anaplastic meningioma appeared on the left side of the skull base at the age of 15, and 50 Gy/25 fr of postoperative intensity-modulated radiation therapy was performed. Two years later, another meningioma developed in the right cerebellar tent, and 54 Gy/27 fr of SRT was performed. Thirty-three months after re-irradiation, MRI showed a slight increase of the lesion, but no late toxicities are observed. CONCLUSION The follow-up periods are short, however intracranial re-irradiation after radiotherapy for pediatric brain tumors were feasible and effective.

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