Search Tips

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

UID: 10738

Author(s): Shipp, Margaret A., Getz, Gad

Study Description from dbGaP: "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-κB, JAK/STAT and PI3K signaling pathways. EBV- cHLs had a higher prevalence of genetic alterations in the NF-κB 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 ("Aging"), in addition to APOBEC, AID and MSI-associated hypermutation. In particular, the mutational burden in EBV- cHLs was among the highest reported, similar to that of carcinogen-induced tumors. Together, the overall high mutational burden, MSI-associated hypermutation and newly identified genetic alterations represent additional potential bases for the efficacy of PD-1 blockade in cHL. Of note, recurrent cHL alterations including B2M, TNFAIP3, STAT6, GNA13 and XPO1 mutations and 2p/2p15, 6p21.32, 6q23.2 and 9p/9p24.1 copy number alterations were also identified in >20% of primary mediastinal B-cell lymphomas, highlighting shared pathogenetic mechanisms in these diseases (companion manuscript1). Reprinted from Blood Advances 2019;3(23):4065-4080.PMID: 31816062. "
Subject of Study
OncoTree Cancer Type(s)
Classical Hodgkin Lymphoma
Diffuse Large B-Cell Lymphoma, NOS
Hodgkin Lymphoma
Access via dbGaP

478 WXS sequencing run from 324 phenotyped subjects
Accession #: phs000450.v4.p1

Access Restrictions
Application Required
Access Instructions
Full access to this dataset in dbGaP requires authorization through an Authorized Access Portal which can be requested for either 'data download' or 'view only'. Individual level data download requires a project request. With dbGaP DataBrowser approval, users may view the compilation of individual-level data of general research use. Upon approval, data can be downloaded.

A full list of and information about the SRA runs, BioSamples, and experiments is publicly viewable by going to the 'Molecular Datasets' tab and clicking on 'RunSelector' at the bottom of the page. This will take you to the NCBI SRA Run Selector platform. View and download of the datasets themselves, however, still requires authorization through dbGaP.

Publicly available data such as data dictionaries, variable summaries, documents and truncated analysis are available the public download site FTP link. A link for the list of components downloadable from Authorized Access is featured at the bottom of the Authorized Access Section.
Associated Publications
Data Type
Equipment Used
Illumina HiSeq 2000
Illumina HiSeq 2500
Illumina hiseq 3000
Software Used
SRA Toolkit
Dataset Format(s)
Data Tool(s)
Dataset Size
1.81 TB
Data Catalog Record Updated