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Molecular profiling of tumors of the brainstem by sequencing of CSF-derived circulating tumor DNA.

Publication ,  Journal Article
Pan, C; Diplas, BH; Chen, X; Wu, Y; Xiao, X; Jiang, L; Geng, Y; Xu, C; Sun, Y; Zhang, P; Wu, W; Wang, Y; Wu, Z; Zhang, J; Jiao, Y; Yan, H; Zhang, L
Published in: Acta Neuropathol
February 2019

Brainstem gliomas are molecularly heterogeneous diseases, many of which are difficult to safely surgically resect and have limited treatment options due to their eloquent location. These constraints pose challenges to biopsy, which limits the use of routine molecular profiling and identification of personalized therapies. Here, we explored the potential of sequencing of circulating tumor DNA (ctDNA) isolated from the cerebrospinal fluid (CSF) of brainstem glioma patients as a less invasive approach for tumor molecular profiling. CSF was obtained from patients either intraoperatively (91.2%, 52/57), from ventricular-peritoneal shunt (3.5%, 2/57), or by lumbar puncture (5.3%, 3/57), all prior to surgical manipulation of the tumor. Deep sequencing of glioma-associated genes was performed on CSF-derived ctDNA and, where available, matched blood and tumor DNA from 57 patients, including nine medullary and 23 diffuse intrinsic pontine gliomas (DIPG). At least one tumor-specific mutation was detected in over 82.5% of CSF ctDNA samples (47/57). In cases with primary tumors harboring at least one mutation, alterations were identified in the CSF ctDNA of 97.3% of cases (36/37). In over 83% (31/37) of cases, all primary tumor alterations were detected in the CSF, and in 91.9% (34/37) of cases, at least half of the alterations were identified. Among ten patients found to have primary tumors negative for mutations, 30% (3/10) had detectable somatic alterations in the CSF. Finally, mutation detection using plasma ctDNA was less sensitive than sequencing the CSF ctDNA (38% vs. 100%, respectively). Our study indicates that deep sequencing of CSF ctDNA is a reliable technique for detecting tumor-specific alterations in brainstem tumors. This approach may offer an alternative approach to stereotactic biopsy for molecular profiling of brainstem tumors.

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Published In

Acta Neuropathol

DOI

EISSN

1432-0533

Publication Date

February 2019

Volume

137

Issue

2

Start / End Page

297 / 306

Location

Germany

Related Subject Headings

  • Neurology & Neurosurgery
  • Mutation
  • Humans
  • High-Throughput Nucleotide Sequencing
  • Glioma
  • DNA, Neoplasm
  • Circulating Tumor DNA
  • Brain Stem
  • Biomarkers, Tumor
  • 3209 Neurosciences
 

Citation

APA
Chicago
ICMJE
MLA
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Pan, C., Diplas, B. H., Chen, X., Wu, Y., Xiao, X., Jiang, L., … Zhang, L. (2019). Molecular profiling of tumors of the brainstem by sequencing of CSF-derived circulating tumor DNA. Acta Neuropathol, 137(2), 297–306. https://doi.org/10.1007/s00401-018-1936-6
Pan, Changcun, Bill H. Diplas, Xin Chen, Yuliang Wu, Xiong Xiao, Liping Jiang, Yibo Geng, et al. “Molecular profiling of tumors of the brainstem by sequencing of CSF-derived circulating tumor DNA.Acta Neuropathol 137, no. 2 (February 2019): 297–306. https://doi.org/10.1007/s00401-018-1936-6.
Pan C, Diplas BH, Chen X, Wu Y, Xiao X, Jiang L, et al. Molecular profiling of tumors of the brainstem by sequencing of CSF-derived circulating tumor DNA. Acta Neuropathol. 2019 Feb;137(2):297–306.
Pan, Changcun, et al. “Molecular profiling of tumors of the brainstem by sequencing of CSF-derived circulating tumor DNA.Acta Neuropathol, vol. 137, no. 2, Feb. 2019, pp. 297–306. Pubmed, doi:10.1007/s00401-018-1936-6.
Pan C, Diplas BH, Chen X, Wu Y, Xiao X, Jiang L, Geng Y, Xu C, Sun Y, Zhang P, Wu W, Wang Y, Wu Z, Zhang J, Jiao Y, Yan H, Zhang L. Molecular profiling of tumors of the brainstem by sequencing of CSF-derived circulating tumor DNA. Acta Neuropathol. 2019 Feb;137(2):297–306.
Journal cover image

Published In

Acta Neuropathol

DOI

EISSN

1432-0533

Publication Date

February 2019

Volume

137

Issue

2

Start / End Page

297 / 306

Location

Germany

Related Subject Headings

  • Neurology & Neurosurgery
  • Mutation
  • Humans
  • High-Throughput Nucleotide Sequencing
  • Glioma
  • DNA, Neoplasm
  • Circulating Tumor DNA
  • Brain Stem
  • Biomarkers, Tumor
  • 3209 Neurosciences