Liquid biopsy for children with central nervous system tumours: Clinical integration and technical considerations

Stankunaite, Reda; Marshall, Lynley V.; Carceller, Fernando; Chesler, Louis; Hubank, Michael; George, Sally L.

doi:10.3389/fped.2022.957944

Cited by 6 publications

(3 citation statements)

References 95 publications

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“…This is becoming standard of care, to potentially widen treatment options where molecular findings are actionable, to help understand mechanisms of disease resistance and to discover new targets. So called ‘liquid biopsy’ (circulating tumor DNA, ctDNA) monitoring may shed light in this area, although for CNS tumors, collection of CSF for ctDNA (more invasive than collecting blood but less invasive than tumor biopsy) is likely to be more fruitful ( 97 ).…”

Section: Novel Therapeutic Strategiesmentioning

confidence: 99%

Novel therapeutic approaches for pediatric diencephalic tumors: improving functional outcomes

Cockle,

Corley,

Zebian

et al. 2023

Front. Oncol.

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Pediatric diencephalic tumors represent a histopathologically and molecularly diverse group of neoplasms arising in the central part of the brain and involving eloquent structures, including the hypothalamic-pituitary axis (HPA), optic pathway, thalamus, and pineal gland. Presenting symptoms can include significant neurological, endocrine, or visual manifestations which may be exacerbated by injudicious intervention. Upfront multidisciplinary assessment and coordinated management is crucial from the outset to ensure best short- and long-term functional outcomes. In this review we discuss the clinical and pathological features of the neoplastic entities arising in this location, and their management. We emphasize a clear move towards ‘function preserving’ diagnostic and therapeutic approaches with novel toxicity-sparing strategies, including targeted therapies.

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Section: Novel Therapeutic Strategiesmentioning

confidence: 99%

Novel therapeutic approaches for pediatric diencephalic tumors: improving functional outcomes

Cockle,

Corley,

Zebian

et al. 2023

Front. Oncol.

Self Cite

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“…However, for patients with brain tumors, varying amounts of ctDNA have been demonstrated in cfDNA extracted from plasma, and it is thought that the blood–brain barrier might limit the detection of tumor-specific DNA fragments in the blood [ 10 ]. Importantly, recent reports have indicated that significant amounts of cfDNA can be extracted from cerebrospinal fluid (CSF) and that significant amounts of ctDNA can be detected in patients with different types of brain tumors, including pediatric EBT [ 2 , 11 , 12 , 13 , 14 ]. However, to date, only limited data have been reported on the use of cfDNA extracted from CSF for the complete molecular characterization of pediatric EBT [ 12 , 13 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Cell-Free DNA Extracted from CSF for the Molecular Diagnosis of Pediatric Embryonal Brain Tumors

Chicard

Iddir

Planchon

et al. 2023

Cancers

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Background: Liquid biopsies are revolutionary tools used to detect tumor-specific genetic alterations in body fluids, including the use of cell-free DNA (cfDNA) for molecular diagnosis in cancer patients. In brain tumors, cerebrospinal fluid (CSF) cfDNA might be more informative than plasma cfDNA. Here, we assess the use of CSF cfDNA in pediatric embryonal brain tumors (EBT) for molecular diagnosis. Methods: The CSF cfDNA of pediatric patients with medulloblastoma (n = 18), ATRT (n = 3), ETMR (n = 1), CNS NB FOXR2 (n = 2) and pediatric EBT NOS (n = 1) (mean cfDNA concentration 48 ng/mL; range 4–442 ng/mL) and matched tumor genomic DNA were sequenced by WES and/or a targeted sequencing approach to determine single-nucleotide variations (SNVs) and copy number alterations (CNA). A specific capture covering transcription start sites (TSS) of genes of interest was also used for nucleosome footprinting in CSF cfDNA. Results: 15/25 CSF cfDNA samples yielded informative results, with informative CNA and SNVs in 11 and 15 cases, respectively. For cases with paired tumor and CSF cfDNA WES (n = 15), a mean of 83 (range 1–160) shared SNVs were observed, including SNVs in classical medulloblastoma genes such as SMO and KMT2D. Interestingly, tumor-specific SNVs (mean 18; range 1–62) or CSF-specific SNVs (mean 5; range 0–25) were also observed, suggesting clonal heterogeneity. The TSS panel resulted in differential coverage profiles across all 112 studied genes in 7 cases, indicating distinct promoter accessibility. Conclusion: CSF cfDNA sequencing yielded informative results in 60% (15/25) of all cases, with informative results in 83% (15/18) of all cases analyzed by WES. These results pave the way for the implementation of these novel approaches for molecular diagnosis and minimal residual disease monitoring.

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“…For patients with brain tumors, varying amounts of ctDNA have been demonstrated in cfDNA extracted from plasma, and it is thought that the blood-brain barrier might limit the detection of tumor-specific DNA fragments in the blood stream [10]. Importantly recent reports have indicated that cfDNA can be extracted from cerebrospinal fluid (CSF), and that significant amounts of ctDNA can be detected in patients with different types of brain tumors, including pediatric EBT [2,[11][12][13][14]. However, to date only limited data has been reported on the use of cfDNA extracted from CSF for the complete molecular characterization of pediatric EBT [12,13,15].…”

Section: Introductionmentioning

confidence: 99%

Cell Free DNA Extracted From Csf for Molecular Diagnosis of Pediatric Embryonal Brain Tumors

Chicard¹,

Iddir²,

Planchon³

et al. 2023

Preprint

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Background: Liquid biopsies are revolutionary tools to detect tumor-specific genetic alterations in body fluids, and cell-free DNA (cfDNA) can be used for molecular diagnosis in cancer patients. In brain tumors cerebrospinal fluid (CSF) cfDNA might be more informative than plasma cfDNA. Here, we assess the use of CSF cfDNA in pediatric embryonal brain tumors (EBT) for molecular diagnosis. Methods: CSF cfDNA of pediatric patients with medulloblastoma (n=18), ATRT (n=3), ETMR (n=1), CNS NB FOXR2 (n=2) and pediatric EBT NOS (n=1) (mean cfDNA concentration 48 ng/mL; range 4-442 ng/mL) and matched tumor genomic DNA were sequenced by WES, and/or a targeted sequencing approach, to determine single nucleotide variations (SNVs)/copy number alterations (CNA). A specific capture covering transcription start sites (TSS) of genes of interest was used for nucleosome footprinting in CSF cfDNA. Results: 15/25 CSF cfDNA samples yielded informative results, with informative CNA and SNVs in 11 and 15 cases, respectively. For cases with paired tumor and CSF cfDNA WES (n=15), a mean of 83 (range 1-160) shared SNVs was observed, including SNVs in classical medulloblastoma genes such as SMO and KMT2D. Interestingly, tumor-specific SNVs (mean 18; range 1-62) or CSF-specific SNVs (mean 5; range 0-25) were observed suggesting clonal heterogeneity. The TSS panel resulted in differential coverage profiles across all 112 studied genes in 7 cases, indicating distinct promoter accessibility. Conclusion: CSF cfDNA sequencing yielded informative results in 60% of cases (15/25), with WES feasible in 83% (15/18). These results pave the way for implementation of these novel approaches for molecular diagnosis and minimal residual disease monitoring.

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Liquid biopsy for children with central nervous system tumours: Clinical integration and technical considerations

Cited by 6 publications

References 95 publications

Novel therapeutic approaches for pediatric diencephalic tumors: improving functional outcomes

Novel therapeutic approaches for pediatric diencephalic tumors: improving functional outcomes

Cell-Free DNA Extracted from CSF for the Molecular Diagnosis of Pediatric Embryonal Brain Tumors

Cell Free DNA Extracted From Csf for Molecular Diagnosis of Pediatric Embryonal Brain Tumors

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