| Title: |
Genome-wide aneuploidy detected by mFast-SeqS in circulating cell-free DNA is associated with poor response to pembrolizumab in patients with advanced urothelial cancer |
| Authors: |
Mendelaar, Pauline A. J.; Robbrecht, Debbie G. J.; Rijnders, Maud; de Wit, Ronald; de Weerd, Vanja; Deger, Teoman; Westgeest, Hans M.; Aarts, Maureen J. B.; Voortman, Jens; Martens, John W. M.; van der Veldt, Astrid A. M.; Nakauma-González, José Alberto; Wilting, Saskia M.; Lolkema, Martijn |
| Source: |
Mendelaar, P A J, Robbrecht, D G J, Rijnders, M, de Wit, R, de Weerd, V, Deger, T, Westgeest, H M, Aarts, M J B, Voortman, J, Martens, J W M, van der Veldt, A A M, Nakauma-González, J A, Wilting, S M & Lolkema, M 2022, 'Genome-wide aneuploidy detected by mFast-SeqS in circulating cell-free DNA is associated with poor response to pembrolizumab in patients with advanced urothelial cancer', Molecular oncology, vol. 16, no. 10, pp. 2086-2097. https://doi.org/10.1002/1878-0261.13196 |
| Publication Year: |
2022 |
| Description: |
Second-line treatment with immune checkpoint inhibition in patients with metastatic urothelial cancer (mUC) has a low success rate (~ 20%). Circulating tumour-derived DNA (ctDNA) levels may guide patient stratification, provided that an affordable and robust assay is available. Here, we investigate whether the modified fast aneuploidy screening test-sequencing system (mFast-SeqS) may provide such an assay. To this end, mFast-SeqS was performed on cell-free DNA (cfDNA) from 74 patients with mUC prior to treatment with pembrolizumab. Results were associated with corresponding tissue-based profiles, plasma-based variant allele frequencies (VAFs) and clinical response. We found that plasma-derived mFast-SeqS-based aneuploidy scores significantly correlated with those observed in the corresponding tumour tissue as well as with the ctDNA level in the plasma. In multivariate logistic regression analysis, a high aneuploidy score was independently associated with lack of clinical benefit from treatment with pembrolizumab. In conclusion, mFast-SeqS provides a patient-friendly, high-throughput and affordable method to estimate ctDNA level. Following independent validation, this test could be used to stratify mUC patients for response prior to the initiation of treatment with pembrolizumab. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
1574-7891 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/35181986; info:eu-repo/semantics/altIdentifier/pissn/1574-7891 |
| DOI: |
10.1002/1878-0261.13196 |
| Availability: |
https://research.vumc.nl/en/publications/67835768-7ab5-428b-9485-fa5c5e82956e; https://doi.org/10.1002/1878-0261.13196; https://www.scopus.com/pages/publications/85126383380 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.4EDAAE40 |
| Database: |
BASE |