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Blood. 2018 May 31;131(22):2413-2425. doi: 10.1182/blood-2017-11-812073. Epub 2018 Feb 15.

Circulating tumor DNA reveals genetics, clonal evolution, and residual disease in classical Hodgkin lymphoma.

Author information

Institute of Oncology Research, Bellinzona, Switzerland.
Institute of Hematology and.
Division of Pathology, Policlinico Gemelli Foundation, Catholic University of the Sacred Heart, Rome, Italy.
Humanitas Cancer Center, Humanitas Clinical and Research Center, Milan, Italy.
Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy.
Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy.
Institute of Nuclear Medicine, Policlinico Gemelli Foundation, Catholic University of the Sacred Heart, Rome, Italy.
Hematology Unit, Foundation Ca' Granda IRCCS, Ospedale Maggiore Policlinico, Milan, Italy.
Division of Pathology, Department of Health Science, University of Eastern Piedmont, Novara, Italy; and.
Department of Biomedical Sciences, Humanitas University, Milan, Italy.


The rarity of neoplastic cells in the biopsy imposes major technical hurdles that have so far limited genomic studies in classical Hodgkin lymphoma (cHL). By using a highly sensitive and robust deep next-generation sequencing approach for circulating tumor DNA (ctDNA), we aimed to identify the genetics of cHL in different clinical phases, as well as its modifications on treatment. The analysis was based on specimens collected from 80 newly diagnosed and 32 refractory patients with cHL, including longitudinal samples collected under ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy and longitudinal samples from relapsing patients treated with chemotherapy and immunotherapy. ctDNA mirrored Hodgkin and Reed-Sternberg cell genetics, thus establishing ctDNA as an easily accessible source of tumor DNA for cHL genotyping. By identifying STAT6 as the most frequently mutated gene in ∼40% of cases, we refined the current knowledge of cHL genetics. Longitudinal ctDNA profiling identified treatment-dependent patterns of clonal evolution in patients relapsing after chemotherapy and patients maintained in partial remission under immunotherapy. By measuring ctDNA changes during therapy, we propose ctDNA as a radiation-free tool to track residual disease that may integrate positron emission tomography imaging for the early identification of chemorefractory patients with cHL. Collectively, our results provide the proof of concept that ctDNA may serve as a novel precision medicine biomarker in cHL.

[Indexed for MEDLINE]

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