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Distinct Hodgkin lymphoma subtypes defined by noninvasive genomic profiling.
Alig, Stefan K; Shahrokh Esfahani, Mohammad; Garofalo, Andrea; Li, Michael Yu; Rossi, Cédric; Flerlage, Tim; Flerlage, Jamie E; Adams, Ragini; Binkley, Michael S; Shukla, Navika; Jin, Michael C; Olsen, Mari; Telenius, Adèle; Mutter, Jurik A; Schroers-Martin, Joseph G; Sworder, Brian J; Rai, Shinya; King, Daniel A; Schultz, Andre; Bögeholz, Jan; Su, Shengqin; Kathuria, Karan R; Liu, Chih Long; Kang, Xiaoman; Strohband, Maya J; Langfitt, Deanna; Pobre-Piza, Kristine Faye; Surman, Sherri; Tian, Feng; Spina, Valeria; Tousseyn, Thomas; Buedts, Lieselot; Hoppe, Richard; Natkunam, Yasodha; Fornecker, Luc-Matthieu; Castellino, Sharon M; Advani, Ranjana; Rossi, Davide; Lynch, Ryan; Ghesquières, Hervé; Casasnovas, Olivier; Kurtz, David M; Marks, Lianna J; Link, Michael P; André, Marc; Vandenberghe, Peter; Steidl, Christian; Diehn, Maximilian; Alizadeh, Ash A.
Affiliation
  • Alig SK; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Shahrokh Esfahani M; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Garofalo A; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Li MY; Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
  • Rossi C; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Flerlage T; Hematology Department, University Hospital F. Mitterrand and Inserm UMR 1231, Dijon, France.
  • Flerlage JE; Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USA.
  • Adams R; Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
  • Binkley MS; Department of Pediatrics, Division of Pediatric Hematology and Oncology, Stanford University, Stanford, CA, USA.
  • Shukla N; Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA, USA.
  • Jin MC; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Olsen M; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Telenius A; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Mutter JA; Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
  • Schroers-Martin JG; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Sworder BJ; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Rai S; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • King DA; Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
  • Schultz A; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Bögeholz J; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Su S; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Kathuria KR; Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA, USA.
  • Liu CL; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Kang X; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Strohband MJ; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Langfitt D; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Pobre-Piza KF; Department of Bone Marrow Transplant and Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
  • Surman S; Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USA.
  • Tian F; Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USA.
  • Spina V; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Tousseyn T; Laboratory of Molecular Diagnostics, Department of Medical Genetics EOLAB, Bellinzona, Switzerland.
  • Buedts L; Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
  • Hoppe R; Department of Human Genetics, KU Leuven, Leuven, Belgium.
  • Natkunam Y; Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA, USA.
  • Fornecker LM; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Castellino SM; Institut de Cancérologie Strasbourg Europe (ICANS) and University of Strasbourg, Strasbourg, France.
  • Advani R; Department of Pediatrics, Emory University, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA, USA.
  • Rossi D; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Lynch R; Clinic of Hematology, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
  • Ghesquières H; Laboratory of Experimental Hematology, Institute of Oncology Research, Bellinzona, Switzerland.
  • Casasnovas O; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
  • Kurtz DM; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Marks LJ; Department of Hematology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Benite, France.
  • Link MP; Hematology Department, University Hospital F. Mitterrand and Inserm UMR 1231, Dijon, France.
  • André M; Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
  • Vandenberghe P; Department of Pediatrics, Division of Pediatric Hematology and Oncology, Stanford University, Stanford, CA, USA.
  • Steidl C; Department of Pediatrics, Division of Pediatric Hematology and Oncology, Stanford University, Stanford, CA, USA.
  • Diehn M; Department of Haematology, Université Catholique de Louvain, CHU UCL Namur, Yvoir, Belgium.
  • Alizadeh AA; Department of Human Genetics, KU Leuven, Leuven, Belgium.
Nature ; 625(7996): 778-787, 2024 Jan.
Article in En | MEDLINE | ID: mdl-38081297
The scarcity of malignant Hodgkin and Reed-Sternberg cells hampers tissue-based comprehensive genomic profiling of classic Hodgkin lymphoma (cHL). By contrast, liquid biopsies show promise for molecular profiling of cHL due to relatively high circulating tumour DNA (ctDNA) levels1-4. Here we show that the plasma representation of mutations exceeds the bulk tumour representation in most cases, making cHL particularly amenable to noninvasive profiling. Leveraging single-cell transcriptional profiles of cHL tumours, we demonstrate Hodgkin and Reed-Sternberg ctDNA shedding to be shaped by DNASE1L3, whose increased tumour 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 IL-13 signalling and therapeutically targetable with IL-4Rα-blocking antibodies. Finally, using PhasED-seq5, we demonstrate the clinical value of pretreatment 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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hodgkin Disease / Genome, Human / Genomics / Circulating Tumor DNA Limits: Humans Language: En Journal: Nature Year: 2024 Document type: Article Affiliation country: United States Country of publication: United kingdom
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hodgkin Disease / Genome, Human / Genomics / Circulating Tumor DNA Limits: Humans Language: En Journal: Nature Year: 2024 Document type: Article Affiliation country: United States Country of publication: United kingdom