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

Maurizio Martini, Vittoria Rufini, Alessandro Giordano, Luigi Maria Larocca, Stefan Hohaus, Annarosa Cuccaro, Elisa Cupelli, Alessandra Cocomazzi, Salvatore Annunziata, Valeria Spina, Alessio Bruscaggin, Martina Di Trani, Gabriela Forestieri, Martina Manzoni, Adalgisa Condoluci, Alberto Arribas, Lodovico Terzi-Di-Bergamo, Silvia Laura Locatelli, Luca Ceriani, Alden A. MocciaAnastasios Stathis, Luca Nassi, Clara Deambrogi, Fary Diop, Francesca Guidetti, Antonino Neri, Renzo Boldorini, Bernhard Gerber, Francesco Bertoni, Michele Ghielmini, Georg Stüssi, Armando Santoro, Franco Cavalli, Emanuele Zucca, Gianluca Gaidano, Carmelo Carlo-Stella, Davide Rossi

Risultato della ricerca: Contributo in rivistaArticolo in rivista

85 Citazioni (Scopus)

Abstract

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), here we aimed at tracking the genetics of cHL in different clinical phases, and its modifications upon treatment. The analysis was based on specimens collected from 80 newly diagnosed and 32 refractory cHL patients, including longitudinal samples collected under ABVD 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 PET imaging for the early identification of chemorefractory cHL patients. Collectively, our results provide the proof of concept that ctDNA may serve as novel precision medicine biomarker in cHL.
Lingua originaleEnglish
pagine (da-a)blood-2017-11-812073-N/A
RivistaBlood
DOI
Stato di pubblicazionePubblicato - 2018

Keywords

  • Hodgkin lymphoma
  • circulating tumor DNA

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