The Need for Standardization in Next-Generation Sequencing Studies for Classic Hodgkin Lymphoma: A Systematic Review

Abstract

Classic Hodgkin lymphoma (cHL) constitutes a B cell-derived neoplasm defined by a scarce tumoral population, termed Hodgkin and Reed–Sternberg (HRS) cells, submerged into a histologically heterogeneous microenvironment. The paucity of HRS cells has historically hampered genetic studies, rendering the identification of the recurrent genetic lesions and molecular pathways deregulated in this lymphoma difficult. The advent of high-throughput sequencing methods such as next-generation sequencing (NGS) could sensibly optimize the identification of the mutational landscape of cHL. However, there is no current consensus either in the design of panels for targeted NGS or in its most relevant clinical applications. In this work, we systematically review the current state of NGS studies of cHL, stressing the need for standardization both in the candidate genes to be analyzed and the bioinformatic pipelines. As different institutions have developed and implemented their own customized NGS-based protocols, to compare and systematically review the major findings of this ongoing research area could be of added value for centers that routinely perform diagnostic, monitoring and genotyping strategies in cHL samples. The results of this systematic review should contribute to the interdepartmental harmonization and achievement of a consensus in the current clinical applications of NGS studies of cHL.

Whole-slide image analysis identifies a high content of Hodgkin Reed-Sternberg cells and a low content of T lymphocytes in tumor microenvironment as predictors of adverse outcome in patients with classic Hodgkin lymphoma treated with ABVD

“…The integration of functional studies with WSI would, thus, give us a more comprehensive view of the clinical significance of T cells in the natural history of cHL. Recently, our group proposed the adoption of a minimum set of genes recurrently mutated in cHL for Next-Generation Sequencing (NGS) studies in cHL tissue ( 31 ), and the integration of NGS data with WSI information is the subject of ongoing research in our department.…”

Identification of prognostic factors in classic Hodgkin lymphoma by integrating whole slide imaging and next generation sequencing

“…Regarding this, there is a major challenge to achieve an international consensus in the design of NGS panels for the evaluation of lymphomas. 61,62 Currently, customized panels are employed in most of the laboratories, based on the recommendations of national workgroups and related literature. 63 Consequently, it would be interesting to perform this work by using a panel designed specifically for the genomic analysis of cHL.…”

Pathogenic Variants Associated with Epigenetic Control and the NOTCH Pathway Are Frequent in Classic Hodgkin Lymphoma

“…In this study, using a targeted NGS panel specifically designed for cHL research [ 11 ], we sequenced cHL tumor samples obtained at diagnosis from patients achieving a complete metabolic response and compared them with cHL tumor samples from relapsed/refractory cases. Furthermore, we analyzed paired tissue samples obtained at diagnosis and recurrences to describe the pattern of mutation selection and clonal evolution during the course of the disease.…”