Table Info

Table 2.

Origins of testing ctDNA markers in glioblastomas

Year	Gene	Variation	Source	Method	Tumor
2003 [15]	MGMT	Methylation	Serum	MS-PCR	GBM
2006 [33]			Plasma	MS-PCR	GBM, AA
2010 [34]			Serum	MS-PCR	Astrocytic tumors (WHO III, IV), oligodendroglial tumors (WHO II, III)
2013 [29]			Serum	MS-PCR	Glial tumors (II, III, IV), meningioma
2003 [15]	p16	Methylation	Serum	MS-PCR	GBM
2006 [33]			Plasma	MS-PCR	GBM, AA, AOA
2003 [15]	DAPK	Methylation	Serum	MS-PCR	GBM
2003 [15]	RASSF1A	Methylation	Serum	MS-PCR	GBM
2013 [29]					Glial tumors (II, III, IV), meningioma
2006 [33]	p73	Methylation	Plasma	MS-PCR	GBM
2010 [34]	PTEN	Methylation	Serum	MS-PCR	Astrocytic tumors (WHO III, IV)
2014 [17]		Mutation	Plasma, serum	Digital PCR, sequencing	Glioma II, AA, GBM
2010 [34]	10q	LOH	Serum	LOH	Astrocytic (WHO III, IV), oligodendroglial (WHO II, III)
2012 [35]	IDH1	Mutation (R132H)	Plasma	Digital PCR	Glioma (WHO grade II, III, IV)
2014 [16]		Mutation	Plasma, serum	Digital PCR, sequencing	Glioma II, AA, GBM
2013 [29]	p15INK4B	Methylation	Serum	MS-PCR	Glial tumors (II, III, IV), meningioma
2013 [29]	p14ARF	Methylation	Serum	MS-PCR	Glial tumors (II, III, IV), meningioma
2014 [16]	TP53	Mutation	Plasma, serum	Digital PCR, sequencing	Glioma II, AA, GBM
2014 [16]	EGFR	Mutation	Plasma, serum	Digital PCR, sequencing	Glioma II, AA, GBM
2014 [16]	PIK3CA	Mutation	Plasma, serum	Digital PCR, sequencing	Glioma II, AA, GBM
2015 [28]	TP53, EPHB1, TERT, PIK3CG, IDH1, ANK, EGFR, PTEN, FTH1, OR51D1	Mutation	CSF (plasma)	ddPCR, MAF	GBM
2015 [27]	Genome	Mutation	CSF	TAS/WES	AA III, PA I, ependymoma, medulloblastoma IV, GBM, LGG II, diffuse astrocytoma
2017 [36]	Gene panels (54, 68, 70 genes) including TP53, EGFR, MET	Mutation	Plasma	NGS	Brain tumors (not specified)
2018 [23]	IDH1, IDH2, TP53, TERT, ATRX, H3F3A, HIST1H3B	Mutation	CSF	Sequencing	Diffuse gliomas
2018 [25]	Genome	SCNAs and fragmentation	CSF	WGS	Glioma
2018 [37]	TERT	Mutation	CSF (plasma)	PCR, sequencing	GBM
2019 [38]	Genome including TP53, JAK2, NF1, EGFR, BRAF, IDH1, NRAS, GNAS, ATM	Mutation	Plasma	NGS	Astrocytic/oligodendral tumors grades I–IV, including GBM, medulloblastoma, meningioma, and ependymoma
2019 [24]	P19Q, IDH1, CIC, ATRX, TP53	Mutation	CSF	NGS	LGG, GBM

MS-PCR: methylation-sensitive PCR; AA: anaplastic astrocytoma; AOA: anaplastic oligoastrocytoma; DAPK: death-associated protein kinase; RASSF1A: ras association domain family 1 isoform A; LOH: loss of heterozygosity; PIK3CA: phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha; PIK3CG: phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit gamma; EPHB1: ephrin type-b receptor 1; OR51D1: olfactory receptor family 51 subfamily D member 1; TERT: telomerase reverse transcriptase; ANK: amplified natural killer; FTH1: ferritin heavy chain 1; ddPCR: droplet digital PCR; MAF: mutant allelic frequency; TAS: targeted amplicon sequencing; WES: whole exome sequencing; LGG: low-grade glioma; NGS: next generation sequencing; ATRX: alpha-thalassemia/mental retardation syndrome X-linked; H3F3A: histone 3.3 gene variant A; HIST1H3B: histone 3.1 gene; SCNA: somatic copy-number alterations; WGS: whole-genome sequencing; JAK2: janus kinase 2; NF1: neurofibromatosis type 1; BRAF: v-Raf murine sarcoma viral oncogene homolog B; NRAS: neuroblastoma RAS (viral oncogene homolog of rat sarcoma virus); GNAS: G protein alpha(s); ATM: Ataxia telangiectasia mutated; 1P19Q: 1p/19q codeletion of chromosome arms; CIC: capicua (Catalan: head-and-tail), a Drosophila homologue gene for a transcription repression factor

Declarations

Acknowledgments

We gratefully acknowledge the introduction into the field of brain tumor research by Otmar D. Wiestler and the late Paul Kleihues, as well as discussions with Irving L. Weissman and Eugene C. Butcher on immune and tumor cell migration and metastasis, and Catherine Alix-Panabières on liquid biopsy.

Author contributions

RHE: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. MS: Conceptualization, Investigation, Writing—review & editing. Both of the authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

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