Genomic Analyses of Flow-sorted Hodgkin Reed Sternberg Cells Reveal Complementary Mechanisms of Immune Evasion.

Study ID Alternative Stable ID Type
phs000450 Case Set

Study Description

Classical Hodgkin lymphoma (cHL) is composed of rare malignant Hodgkin Reed Sternberg (HRS) cells within an extensive, but ineffective, inflammatory/immune cell infiltrate. HRS cells exhibit near-universal somatic copy gains of chromosome 9p/9p24.1 which increase expression of the PD-1 ligands. To define genetic mechanisms of response and resistance to PD-1 blockade and identify complementary treatment targets, we performed whole exome sequencing of flow cytometry-sorted HRS cells from 23 excisional biopsies of newly diagnosed cHLs including 8 EBV+ tumors. We identified significantly mutated cancer candidate genes (CCGs) as well as somatic copy number alterations and structural variations and characterized their contribution to disease-defining immune evasion mechanisms and NF-KB, JAK/STAT and PI3K signaling pathways. EBV- cHLs had a higher prevalence of genetic alterations in the NF-KB and MHC class I antigen presentation pathways. In this young cHL cohort (median age of 26), we identified a predominant mutational signature of spontaneous deamination of CpGs ... (Show More)

Archive Link Archive Accession
dbGaP phs000450

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