Next-generation sequencing-based monitoring of circulating tumor DNA reveals clonotypic heterogeneity in untreated PTCL
| Autor: | Erik Yusko, Mark Roschewski, Stefania Pittaluga, Nicole Lucas, Milos D. Miljkovic, Christopher Melani, Elaine S. Jaffe, Allison P. Jacob, Wyndham H. Wilson, Rahul Lakhotia |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Oncology
medicine.medical_specialty business.industry T cell T-cell receptor High-Throughput Nucleotide Sequencing Lymphoma T-Cell Peripheral Hematology Serum samples medicine.disease DNA sequencing Lymphoma Circulating Tumor DNA medicine.anatomical_structure Circulating tumor DNA Internal medicine Clinical heterogeneity medicine Humans In patient Lymphoma Large B-Cell Diffuse Neoplasm Recurrence Local business |
| Zdroj: | Blood advances. 5(20) |
| ISSN: | 2473-9537 |
| Popis: | Peripheral T-cell lymphomas (PTCLs) have marked biologic and clinical heterogeneity, which confounds treatment decisions. Advances in circulating tumor DNA (ctDNA) assays using next-generation sequencing (NGS) have improved the detection of molecular relapse and driver mutations in diffuse large B-cell lymphoma and show the potential utility of ctDNA across lymphomas. We investigated NGS-based monitoring of T-cell receptor (TCR) sequences in patients with PTCL undergoing frontline treatment. Of 45 patients, 34 (76%) had tumor-specific clonotypes of the TCRβ or TCRγ genes identified, which included 18 (86%) from baseline tissue and 16 (67%) from baseline serum. Twenty-five (74%) patients had both TCRβ and TCRγ clonotypes, 23 (68%) had more than 1 TCRγ clonotype, and 4 (9%) had multiple TCRβ or TCRγ clonotypes, demonstrating significant intrapatient clonotypic heterogeneity. Among 24 patients with available serial serum samples during treatment, 9 (38%) cleared ctDNA after 2 cycles of therapy, and 11 (46%) had detectable ctDNA at the end of treatment. Patients with detectable ctDNA after therapy showed a trend toward worse survival. Notably, 2 patients with persistently detectable ctDNA after therapy remained in remission with 10 years of follow-up. Clonotypic heterogeneity in tumors and persistence, despite long-term remission, suggests variability in oncological potential. This trial was registered at www.clinicaltrials.gov as #NCT00001337. |
| Databáze: | OpenAIRE |
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