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During the 14th International Conference on Malignant Lymphoma (ICML) held in Lugano, Switzerland, a Hodgkin Lymphoma Session, co-chaired by V. Diehl (University of Cologne, Germany) and A. Pavlovsky (Pavlovsky Center for Hematology, Buenos Aires), took place on Thursday 15th June.
During this session, D. Rossi from the Institute of Oncology Research, Bellinzona, Switzerland, gave a talk on genotyping classical Hodgkin Lymphoma (cHL) using a liquid biopsy (abstract #052).
Thus far, the mutational profile of cHL is poorly characterized and the genetics of refractory disease have not been fully elucidated. Genotyping of tumor tissue is challenging (i.e. tumor representation, FFPE) and interim PET is neither 100% sensitive or specific for defining ultimate patient outcome.
Liquid biopsy is a source of tumor DNA for Lymphoma genotyping. Plasma cell free DNA is easily accessible, allows for real time monitoring, and has already been tested in DLBCL.
The study presented by Rossi aimed to:
The study included plasma cfDNA and germline (g)DNA from 29 patients with treatment naïve and 15 patients with chemo-refractory cHL. Paired gDNA from tumor tissue biopsies was available for 17 patients, including 3 cases for which Reed-Sternberg (RS) enriched areas were macro-dissected. Plasma cfDNA, normal gDNA, and tumor gDNA were subjected to targeted ultra-deep Next Generation Sequencing (NGS) by using CAPP-seq and Illumina platforms (sensitivity of 3x10-3).
Davide Rossi concluded the talk by stating that cHL can successfully be genotyped using plasma cfDNA. STAT6, TNFAIP3, and ITPKB are frequently (>20%) mutated in cHL. ITPKB mutations (approximately in 30% of cases) associate with pAKT and resistance to PI3K inhibitors. cHL refractoriness does not associate with TP53 mutations but is enriched with TET2 mutations. Clonal evolution in cHL follows a branching pattern. Lastly, dynamic changes in tumor cfDNA may complement imaging in anticipating ABVD outcome.
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