Molecular tumor analysis and liquid biopsy: a feasibility investigation analyzing circulating tumor DNA in patients with central nervous system lymphomas

Table 2 Results of Routine Pathologic Evaluation, Tumor Tissue Analysis und Analysis of cfDNA

Nr.	Routine Pathologic Evaluation		Tumor Tissue – NGS Panel Analysis			cfDNA - Plasma		cfDNA – CSF
	Histopathologic Diagnosis	Tumor cells in CSF	Number of somatic mutations ^a	Selected Mutation for Assay (missense)	MAF (TC)	Tumor cfDNA	MAF	Tumor cfDNA	MAF
1	Primary B-Cell Lymphoma	no	24	EP400-c.7792G > A (Chr.12)	0.32^b (50%)	no^d	n.a.^d	no^d	n.a. ^d
2	Primary B-Cell Lymphoma	no	1	MDM2-c.4G > A (Chr.12)	0.34^b (50%)	no^d	n.a. ^d	no^d	n.a. ^d
3	Primary B-Cell Lymphoma	no	20	TP53-c.845G > A (Chr.17)	0.44 (90%)	yes	0.04	yes	0.49
4	Primary B-Cell Lymphoma	yes	26	BCL10-c.677G > C (Chr.1)	0.47 (90%)	yes	0.004	yes	0.47
5	Primary B-Cell Lymphoma	yes	32	ETV6-c.1196G > A (Chr.12)	0.52^b,c (50%)	yes	0.02	yes	0.99 ^b,c
6	Unspecific Hypervascularity/No malignancy	no	0	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.

^a2 independent somatic mutations within the same gene are counted as 2 mutations. Complex somatic aberrations on the same allele are counted as 1 mutation
^bLoss of wt allele
^cAdditional duplication of the mutated allele
^dIsolation of cfDNA failed in these samples, probably due to the isolation kit (see text)
Nomenclature of the mutations is according to NM_015409.4 (EP400), NM_002392.5 (MDM2), NM_001126114.2 (TP53), NM_003921.4 (BCL10), NM_001987.4 (ETV6)
TC tumor content (calculated based on the NAFs of various somatic mutations and single nucleotide variants both present in tumor and reference tissue)
MAF mutant allele frequency = the frequency with which the mutated allele occurs in the sequencing (1 equals 100%). The observed frequencies are influenced by the tumor content and do not correlate directly with the mutation frequency in the tumor (real frequency = tumor content x MAF). The MAF is also influenced by copy number aberrations

ISSN: 1471-2407