dc.contributor.author
Liebs, Sandra
dc.contributor.author
Eder, Theresa
dc.contributor.author
Klauschen, Frederick
dc.contributor.author
Schütte, Moritz
dc.contributor.author
Yaspo, Marie-Laure
dc.contributor.author
Keilholz, Ulrich
dc.contributor.author
Tinhofer, Ingeborg
dc.contributor.author
Kidess-Sigal, Evelyn
dc.contributor.author
Braunholz, Diana
dc.date.accessioned
2023-07-18T12:08:27Z
dc.date.available
2023-07-18T12:08:27Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/40146
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-39868
dc.description.abstract
Genetic investigation of tumor heterogeneity and clonal evolution in solid cancers could be assisted by the analysis of liquid biopsies. However, tumors of various entities might release different quantities of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) into the bloodstream, potentially limiting the diagnostic potential of liquid biopsy in distinct tumor histologies. Patients with advanced colorectal cancer (CRC), head and neck squamous cell carcinoma (HNSCC), and melanoma (MEL) were enrolled in the study, representing tumors with different metastatic patterns. Mutation profiles of cfDNA, CTCs, and tumor tissue were assessed by panel sequencing, targeting 327 cancer-related genes. In total, 30 tissue, 18 cfDNA, and 7 CTC samples from 18 patients were sequenced. Best concordance between the mutation profile of tissue and cfDNA was achieved in CRC and MEL, possibly due to the remarkable heterogeneity of HNSCC (63%, 55% and 11%, respectively). Concordance especially depended on the amount of cfDNA used for library preparation. While 21 of 27 (78%) tissue mutations were retrieved in high-input cfDNA samples (30-100 ng, N = 8), only 4 of 65 (6%) could be detected in low-input samples (<30 ng, N = 10). CTCs were detected in 13 of 18 patients (72%). However, downstream analysis was limited by poor DNA quality, allowing targeted sequencing of only seven CTC samples isolated from four patients. Only one CTC sample reflected the mutation profile of the respective tumor. Private mutations, which were detected in CTCs but not in tissue, suggested the presence of rare subclones. Our pilot study demonstrated superiority of cfDNA- compared to CTC-based mutation profiling. It was further shown that CTCs may serve as additional means to detect rare subclones possibly involved in treatment resistance. Both findings require validation in a larger patient cohort.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
liquid biopsies
en
dc.subject
mutational profile
en
dc.subject
tumor tissue
en
dc.subject
cancer entities
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Applicability of liquid biopsies to represent the mutational profile of tumor tissue from different cancer entities
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1038/s41388-021-01928-w
dcterms.bibliographicCitation.journaltitle
Oncogene
dcterms.bibliographicCitation.number
33
dcterms.bibliographicCitation.originalpublishername
Springer Nature
dcterms.bibliographicCitation.pagestart
5204
dcterms.bibliographicCitation.pageend
5212
dcterms.bibliographicCitation.volume
40
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.funding
Springer Nature DEAL
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
34230613
dcterms.isPartOf.issn
0950-9232
dcterms.isPartOf.eissn
1476-5594