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000287463 245__ $$aCerebrospinal fluid cfDNA sequencing for classification of central nervous system glioma.
000287463 260__ $$aPhiladelphia, Pa. [u.a.]$$bAACR$$c2024
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000287463 520__ $$aPrimary central nervous system (CNS) gliomas can be classified by characteristic genetic alterations. In addition to solid tissue obtained via surgery or biopsy, cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) is an alternative source of material for genomic analyses.We performed targeted next-generation sequencing (NGS) of CSF cfDNA in a representative cohort of 85 patients presenting at two neurooncological centers with suspicion of primary or recurrent glioma. Copy-number variation (CNV) profiles, single nucleotide variants (SNVs), and small insertions/ deletions (indels) were combined into a molecular-guided tumor classification. Comparison with the solid tumor was performed for 38 cases with matching solid tissue available.Cases were stratified into four groups: glioblastoma (n = 32), other glioma (n = 19), non-malignant (n = 17) and non-diagnostic (n = 17). We introduced a molecular-guided tumor classification, which enabled identification of tumor entities and/ or cancer specific alterations in 75.0 % (n = 24) of glioblastoma and 52.6 % (n = 10) of other glioma cases. The overlap between CSF and matching solid tissue was highest for CNVs (26-48 %) and SNVs at pre-defined gene loci (44 %), followed by SNVs/ indels identified via uninformed variant calling (8-14 %). A molecular-guided tumor classification was possible for 23.5 % (n = 4) of non-diagnostic cases.We developed a targeted sequencing workflow for CSF cfDNA as well as a strategy for interpretation and reporting of sequencing results based on a molecular-guided tumor classification in glioma.
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000287463 7001_ $$0P:(DE-He78)e50ff195896914d35f54ed1bf913e270$$aHoffmann, Dirk Carsten Frieder$$b2$$udkfz
000287463 7001_ $$00000-0001-7987-0444$$aGrassl, Niklas$$b3
000287463 7001_ $$00009-0002-4405-1427$$aGüngör, Cansu$$b4
000287463 7001_ $$0P:(DE-He78)b6273c0ba3ae37a4d3d1c6b084797f2e$$aMeyer, Jochen$$b5$$udkfz
000287463 7001_ $$00009-0001-1528-3889$$aDörner, Laura$$b6
000287463 7001_ $$00009-0001-4651-3659$$aHofmann, Lea$$b7
000287463 7001_ $$00009-0008-1911-5832$$aKelbch, Vanessa$$b8
000287463 7001_ $$0P:(DE-He78)91f2043e3a8b3c5d31ec010fc634b118$$aGöbel, Kirsten$$b9$$udkfz
000287463 7001_ $$aMahmutoglu, Mustafa Ahmed$$b10
000287463 7001_ $$00000-0002-6224-0064$$aVollmuth, Phillipp$$b11
000287463 7001_ $$0P:(DE-He78)79506056c05e539af84edf040f0a93ad$$aPatel, Areeba Jamilkhan$$b12$$udkfz
000287463 7001_ $$0P:(DE-He78)068f2a9a434bde6bdd0b039f6a7ee5d2$$aNguyen, Duy$$b13$$udkfz
000287463 7001_ $$0P:(DE-He78)7a5d9437d9f4f1be08abac88e2018fa6$$aKaulen, Leon$$b14$$udkfz
000287463 7001_ $$0P:(DE-He78)7daa75b87e6d6e291016ecb54f60b6b3$$aMildenberger, Iris$$b15$$udkfz
000287463 7001_ $$0P:(DE-He78)0f9fbf5fd70dad2bba0760cee65c9613$$aSahm, Katharina$$b16$$udkfz
000287463 7001_ $$0P:(DE-He78)5100059e746b377e2e0a37c0e24f6bf7$$aMaass, Kendra$$b17$$udkfz
000287463 7001_ $$0P:(DE-He78)a7c1bbac024fa232d9c6b78443328d9d$$aPajtler, Kristian$$b18$$udkfz
000287463 7001_ $$00009-0006-5203-8619$$aShankar, Ganesh M$$b19
000287463 7001_ $$aWeiler, Markus$$b20
000287463 7001_ $$00000-0002-5389-3338$$aWildemann, Brigitte$$b21
000287463 7001_ $$0P:(DE-He78)6c294453ee36ad59deddc5494fa6aa4b$$aWinkler, Frank$$b22$$udkfz
000287463 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b23$$udkfz
000287463 7001_ $$0P:(DE-He78)5ef8651b0f857b9c640aa5b1498c43b5$$aPlatten, Michael$$b24$$udkfz
000287463 7001_ $$0P:(DE-He78)92e9783ca7025f36ce14e12cd348d2ee$$aWick, Wolfgang$$b25$$udkfz
000287463 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b26$$eLast author$$udkfz
000287463 7001_ $$0P:(DE-He78)5c2c9cbe6ce72553684d82d94aebdadd$$aKessler, Tobias$$b27$$eLast author$$udkfz
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