Brain Tumor Mutations Detected in Cerebral Spinal Fluid

Pan, Wenying; Gu, Wei; Nagpal, Seema; Gephart, Melanie Hayden; Quake, Stephen R.

doi:10.1373/clinchem.2014.235457

Cited by 246 publications

(208 citation statements)

References 27 publications

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“…Therefore, based on the study above and our current study, the blood-brain barrier does not preclude primary brain tumors from shedding ctDNA into the circulation (31). For patients with primary brain cancers, cerebrospinal fluid may also serve as an alternative "liquid biopsy" (32).…”

Section: Discussionmentioning

confidence: 99%

Use of Liquid Biopsies in Clinical Oncology: Pilot Experience in 168 Patients

Schwaederlé¹,

Husain²,

Fanta³

et al. 2016

Clinical Cancer Research

123

124

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Purpose: There is a growing interest in using circulating tumor DNA (ctDNA) testing in patients with cancer. Experimental Design: A total of 168 patients with diverse cancers were analyzed. Patients had digital next-generation sequencing (54 cancer-related gene panel including amplifications in ERBB2, EGFR, and MET) performed on their plasma. Type of genomic alterations, potential actionability, concordance with tissue testing, and patient outcome were examined. Results: Fifty-eight percent of patients (98/168) had ≥1 ctDNA alteration(s). Of the 98 patients with alterations, 71.4% had ≥ 1 alteration potentially actionable by an FDA-approved drug. The median time interval between the tissue biopsy and the blood draw was 2.7 months for patients with ≥ 1 alteration in common compared with 14.4 months (P = 0.006) for the patients in whom no common alterations were identified in the tissue and plasma. Overall concordance rates for tissue and ctDNA were 70.3% for TP53 and EGFR, 88.1% for PIK3CA, and 93.1% for ERBB2 alterations. There was a significant correlation between the cases with ≥ 1 alteration with ctDNA ≥ 5% and shorter survival (median = 4.03 months vs. not reached at median follow-up of 6.1 months; P < 0.001). Finally, 5 of the 12 evaluable patients (42%) matched to a treatment targeting an alteration(s) detected in their ctDNA test achieved stable disease ≥ 6 months/partial remission compared with 2 of 28 patients (7.1%) for the unmatched patients, P = 0.02. Conclusions: Our initial study demonstrates that ctDNA tests provide information complementary to that in tissue biopsies and may be useful in determining prognosis and treatment. Clin Cancer Res; 22(22); 5497–505. ©2016 AACR.

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Section: Discussionmentioning

confidence: 99%

Use of Liquid Biopsies in Clinical Oncology: Pilot Experience in 168 Patients

Schwaederlé¹,

Husain²,

Fanta³

et al. 2016

Clinical Cancer Research

123

124

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“…Brain tumor mutations can now be detected in the cell-free DNA of cerebrospinal fluid. 64,91 In a recent proof-of-principle study, elevated cell-free RNA transcripts of APP and PSD3 were identified in the serum of patients diagnosed with Alzheimer's disease, while transcripts associated with neural development were detectable in peripheral blood of women during pregnancy.…”

Section: Work In Progressmentioning

confidence: 99%

Radiation-induced brain injury: low-hanging fruit for neuroregeneration

Burns

Awad

et al. 2016

FOC

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Brain radiation is a fundamental tool in neurooncology to improve local tumor control, but it leads to profound and progressive impairments in cognitive function. Increased attention to quality of life in neurooncology has accelerated efforts to understand and ameliorate radiation-induced cognitive sequelae. Such progress has coincided with a new understanding of the role of CNS progenitor cell populations in normal cognition and in their potential utility for the treatment of neurological diseases. The irradiated brain exhibits a host of biochemical and cellular derangements, including loss of endogenous neurogenesis, demyelination, and ablation of endogenous oligodendrocyte progenitor cells. These changes, in combination with a state of chronic neuroinflammation, underlie impairments in memory, attention, executive function, and acquisition of motor and language skills. Animal models of radiation-induced brain injury have demonstrated a robust capacity of both neural stem cells and oligodendrocyte progenitor cells to restore cognitive function after brain irradiation, likely through a combination of cell replacement and trophic effects. Oligodendrocyte progenitor cells exhibit a remarkable capacity to migrate, integrate, and functionally remyelinate damaged white matter tracts in a variety of preclinical models. The authors here critically address the opportunities and challenges in translating regenerative cell therapies from rodents to humans. Although valiant attempts to translate neuroprotective therapies in recent decades have almost uniformly failed, the authors make the case that harnessing human radiation-induced brain injury as a scientific tool represents a unique opportunity to both successfully translate a neuroregenerative therapy and to acquire tools to facilitate future restorative therapies for human traumatic and degenerative diseases of the central nervous system.

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“…However, due to blood-brain barrier (BBB), patients with brain tumors do not present with or present with only low amounts of ctDNA in plasma (17). Recently, a few studies have demonstrated that tumor mutations are detectable in the CSF of patients with various primary and metastatic brain tumors, and ctDNA in CSF recapitulates the genomic landscape of brain tumors better than plasma (18)(19)(20). Therefore, CSF may serve as liquid biopsy to monitor brain tumor evolution.…”

Section: Introductionmentioning

confidence: 99%

Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non–Small Cell Lung Cancer

Fan

Zhu²,

et al. 2018

Clinical Cancer Research

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Purpose: Leptomeningeal metastasis (LM) is a detrimental complication of non-small cell lung cancer (NSCLC) and associated with poor prognosis. However, the underlying mechanisms of the metastasis process are still poorly understood.Experimental Design: We performed next-generation panel sequencing of primary tumor tissue, cerebrospinal fluid (CSF), and matched normal controls from epidermal growth factor receptor (EGFR) mutation-positive NSCLC patients with LM.Results: The status of EGFR-activating mutations was highly concordant between primary tumor and CSF. PIK3CA aberrations were high in these patients, implicating an association with LM risk. Intriguingly, low overlapping of somatic protein-changing variants was observed between paired CSF and primary lesions, exhibiting tumor heterogeneity and genetic divergence. Moreover, genes with CSF-recurrent genomic alterations were predominantly involved in cell-cycle regulation and DNA-damage response (DDR), suggesting a role of the pathway in LM development.Conclusions: Our study has shed light on the genomic variations of NSCLC-LM, demonstrated genetic heterogeneity and divergence, uncovered involvement of cell-cycle and DDR pathway, and paved the way for potential therapeutic approaches to this unmet medical need.

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Brain Tumor Mutations Detected in Cerebral Spinal Fluid

Cited by 246 publications

References 27 publications

Use of Liquid Biopsies in Clinical Oncology: Pilot Experience in 168 Patients

Use of Liquid Biopsies in Clinical Oncology: Pilot Experience in 168 Patients

Radiation-induced brain injury: low-hanging fruit for neuroregeneration

Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non–Small Cell Lung Cancer

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