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Circulating Genomic Determinants of Treatment Failure in Hodgkin Lymphoma
dbGaP
Data Resource:  dbGaP
Point of Contact:  
Ash A. Alizadeh, MD, PhD,  
Project

About This Dataset
In this study, we show that the plasma representation of mutations exceeds the bulk tumor representation in most cases, making classic Hodgkin Lymphoma (cHL) particularly amenable to noninvasive profiling. Leveraging single-cell transcriptional profiles of cHL tumors, we demonstrate hazard ratios (HRs) circulating tumor DNA (ctDNA) shedding to be shaped by DNASE1L3, whose increased tumor microenvironment-derived expression drives high ctDNA concentrations. Using this insight, we comprehensively profile 366 patients, revealing two distinct cHL genomic subtypes with characteristic clinical and prognostic correlates, as well as distinct transcriptional and immunological profiles. Furthermore, we identify a novel class of truncating IL4R-mutations that are dependent on IL13 signaling and therapeutically targetable with IL4R blocking antibodies. Finally, we demonstrate the clinical value of pre- and on-treatment ctDNA levels for longitudinally refining cHL risk prediction, and for detection of radiographically occult minimal residual disease. Collectively, these results support the utility of noninvasive strategies for genotyping and dynamic monitoring of cHL as well as capturing molecularly distinct subtypes with diagnostic, prognostic, and therapeutic potential. All patients were treated at cancer centers across Europe and North America between 2011 and 2020. The following 3 cancer centers--Stanford, CA, USA; Bellinzona, Switzerland; and Leuven, Belgium--were included.
Core Data Elements
Number of Cases
445
Case Sex
Female (200); Male (220); Unknown (25)
Case Age At Diagnosis
0 to 4 years (2); 5 to 9 years (5); 10 to 14 years (25); 15 to 19 years (43); 20 to 24 years (51); 25 to 29 years (40); 30 to 34 years (40); 35 to 39 years (20); Greater than 39 years (136); Unknown (83)
Case Race
Not Reported (445)
Case Ethnicity
Not Reported (445)
Case Disease Diagnosis
Hodgkin Lymphoma (445)
Case Tumor Site
Not Reported (445)
Number of Samples
1,281
Sample Analyte Type
DNA (1,200); RNA (81)
Sample Anatomic Site
Lymph Node (191); Peripheral Blood (290); Plasma (800)
Sample Is Normal
Yes (1,100); No (181)
Additional Data Elements
CLINICAL TRIAL IDENTIFIER
DBGAP STUDY IDENTIFIER
Grant Information
R01CA257655
Circulating Genomic Determinants of Treatment Failure in Hodgkin Lymphoma
Published In
https://doi.org/10.1038/s41586-023-06903-x
Charts
Male (220); Female (200); Unknown (25)
220Male