Comprehensive DSRCT multi-omics analyses unveil CACNA2D2 as a diagnostic hallmark and super-enhancer-driven EWSR1::WT1 signature gene

Florian Henning Geyer; Alina Ritter; Seneca Kinn-Gurzo; Tobias Faehling; Jing Li; Armin Jarosch; Carine Ngo; Endrit Vinca; Karim Aljakouch; Azhar Orynbek; Shunya Ohmura; Thomas Kirchner; Roland Imle; Laura Romero-Pérez; Juan Díaz-Martín; Stefanie Bertram; Enrique de Álava; Clémence Henon; Sophie Postel-Vilnay; Ana Banito; Martin Sill; Yvonne Versleijen-Jonkers; Benjamin Friedrich Berthold Mayer; Martin Ebinger; Monika Sparber-Sauer; Sabine Stegmaier; Daniel Baumhoer; Wolfgang Hartmann; Jeroen Krijgsveld; David Horst; Olivier Delattre; Patrick Joseph Grohar; Thomas Georg Phillip Grünewald; Florencia Cidre-Aranaz

doi:10.1002/cac2.70015

Cancer Communications ›› 2025, Vol. 45 ›› Issue (6) : 702 -708. DOI: 10.1002/cac2.70015

LETTER TO THE JOURNAL

Comprehensive DSRCT multi-omics analyses unveil CACNA2D2 as a diagnostic hallmark and super-enhancer-driven EWSR1::WT1 signature gene

Florian Henning Geyer ¹^,²^,³^,⁴
, Alina Ritter ¹^,²^,³^,⁴
, Seneca Kinn-Gurzo ⁵
, Tobias Faehling ¹^,²^,³^,⁴
, Jing Li ¹^,²^,³
, Armin Jarosch ⁶^,⁷
, Carine Ngo ⁸
, Endrit Vinca ¹^,²^,³
, Karim Aljakouch ⁹
, Azhar Orynbek ⁹
, Shunya Ohmura ¹^,²^,³
, Thomas Kirchner ¹⁰
, Roland Imle ¹^,²^,¹¹^,¹²
, Laura Romero-Pérez ¹³^,¹⁴
, Juan Díaz-Martín ¹³
, Stefanie Bertram ¹⁵
, Enrique de Álava ¹³^,¹⁶^,¹⁷
, Clémence Henon ¹⁸
, Sophie Postel-Vilnay ¹⁸^,¹⁹
, Ana Banito ¹^,²^,¹²
, Martin Sill ¹^,²^,²⁰
, Yvonne Versleijen-Jonkers ²¹
, Benjamin Friedrich Berthold Mayer ²²
, Martin Ebinger ²³
, Monika Sparber-Sauer ²⁴^,²⁵
, Sabine Stegmaier ²⁴
, Daniel Baumhoer ²⁶
, Wolfgang Hartmann ²⁷
, Jeroen Krijgsveld ⁹
, David Horst ⁶^,⁷
, Olivier Delattre ²⁸
, Patrick Joseph Grohar ⁵
, Thomas Georg Phillip Grünewald ¹^,²^,³^,²⁹
, Florencia Cidre-Aranaz ¹^,²^,³

Author information +

¹. Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany

². National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany

³. Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany

⁴. Faculty of Medicine, Heidelberg University, Heidelberg, Germany

⁵. Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

⁶. Department of Pathology, Charité-University Medicine Berlin, Corporate Member of Freie Universität Berlin and Humboldt-University of Berlin, Berlin, Germany

⁷. German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Centre (DKFZ), Heidelberg, Germany

⁸. Sarcoma Unit, Gustave Roussy Cancer Campus, Villejuif, France

⁹. Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), and Heidelberg University Medical Faculty, Heidelberg, Germany

¹⁰. Institute of Pathology, Faculty of Medicine, Ludwig-Maximilian-University of Munich, Munich, Germany

¹¹. Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany

¹². Soft-Tissue Sarcoma Junior Research Group, DKFZ, Heidelberg, Germany

¹³. Institute of Biomedicine of Seville (IBiS)/University Hospital Virgen del Rocío/CSIC/University of Seville/CIBERONC, Seville, Spain

¹⁴. Department of Human Anatomy and Embryology, Faculty of Medicine, University of Seville, Seville, Spain

¹⁵. Institute of Pathology, University Hospital Essen, Essen, Germany

¹⁶. Department of Normal and Pathological Histology and Cytology, Faculty of Medicine, University of Seville, Seville, Spain

¹⁷. Department of Pathology, University Hospital Virgen del Rocío, Pathology Unit, Seville, Spain

¹⁸. ERC Chromatin Remodeling, DNA Repair, and Epigenetics Laboratory, ARC Team for Fundamental Research, INSERM U981, and Drug Development Department, Gustave Roussy, Villejuif, France

¹⁹. University College of London Cancer Institute, London, UK

²⁰. Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany

²¹. Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands

²². Department of Pediatric Surgery and Pediatric Urology, University Children's Hospital, Tübingen, Germany

²³. Department of Pediatric Hematology and Oncology, University Children's Hospital, Tuebingen, Germany

²⁴. Stuttgart University Hospital gKAöR, Olgahospital, Stuttgart Cancer Center, Center for Child, Adolescent, and Women's Medicine, Pediatrics 5 (Pediatric Oncology, Hematology, Immunology), Stuttgart, Germany

²⁵. University of Medicine Tübingen, Tübingen, Germany

²⁶. Bone Tumor Reference Centre, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, and Basel Research Centre of Child Health, Basel, Switzerland

²⁷. Gerhard-Domagk-Institute of Pathology, University of Muenster, Muenster, Germany

²⁸. Diversity and Plasticity of Pediatric Tumors, Paris Sciences and Letters University, SIREDO Oncology Centre, Institut Curie, Paris, France

²⁹. Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany

florencia.cidrearanaz@dkfz.de

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Florian Henning Geyer, Alina Ritter, Seneca Kinn-Gurzo, Tobias Faehling, Jing Li, Armin Jarosch, Carine Ngo, Endrit Vinca, Karim Aljakouch, Azhar Orynbek, Shunya Ohmura, Thomas Kirchner, Roland Imle, Laura Romero-Pérez, Juan Díaz-Martín, Stefanie Bertram, Enrique de Álava, Clémence Henon, Sophie Postel-Vilnay, Ana Banito, Martin Sill, Yvonne Versleijen-Jonkers, Benjamin Friedrich Berthold Mayer, Martin Ebinger, Monika Sparber-Sauer, Sabine Stegmaier, Daniel Baumhoer, Wolfgang Hartmann, Jeroen Krijgsveld, David Horst, Olivier Delattre, Patrick Joseph Grohar, Thomas Georg Phillip Grünewald, Florencia Cidre-Aranaz. Comprehensive DSRCT multi-omics analyses unveil CACNA2D2 as a diagnostic hallmark and super-enhancer-driven EWSR1::WT1 signature gene. Cancer Communications, 2025, 45(6): 702-708 DOI:10.1002/cac2.70015

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References

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[1]	Cidre-Aranaz F, Watson S, Amatruda JF, Nakamura T, Delattre O, de Alava E, et al. Small round cell sarcomas. Nat Rev Dis Primers. 2022; 8(1): 1–22.

[2]	de Alava E, Marcilla D. Birth and evolution of the desmoplastic small round-cell tumor. Semin Diagn Pathol. 2016; 33(5): 254–61.

[3]	Ladanyi M, Gerald W. Fusion of the EWS and WT1 Genes in the Desmoplastic Small Round Cell Tumor. Cancer Res. 1994; 54(11): 2837–40.

[4]	Gedminas JM, Chasse MH, Mcbrairty M, Beddows I, Kitchen-Goosen SM, Grohar PJ. Desmoplastic small round cell tumor is dependent on the EWS-WT1 transcription factor. Oncogenesis. 2020; 9(4): 41.

[5]	Hingorani P, Dinu V, Zhang X, Lei H, Shern JF, Park J, et al. Transcriptome analysis of desmoplastic small round cell tumors identifies actionable therapeutic targets: a report from the Children's Oncology Group. Sci Reports. 2020; 10(1): 12318.

[6]	Boulay G, Broye LC, Dong R, Iyer S, Sanalkumar R, Xing Y-H, et al. EWS-WT1 fusion isoforms establish oncogenic programs and therapeutic vulnerabilities in desmoplastic small round cell tumors. Nat Commun. 2024; 15(1): 7460.

[7]	Magrath JW, Sampath SS, Flinchum DA, Hartono AB, Goldberg IN, Boehling JR, et al. Comprehensive Transcriptomic Analysis of EWSR1::WT1 Targets Identifies CDK4/6 Inhibitors as an Effective Therapy for Desmoplastic Small Round Cell Tumors. Cancer Res. 2024; 84(9): 1426–42.

[8]	Hartono AB, Kang H-J, Shi L, Phipps W, Ungerleider N, Giardina A, et al. Salt-Inducible Kinase 1 is a potential therapeutic target in Desmoplastic Small Round Cell Tumor. Oncogenesis. 2022; 11(1): 1–10.

[9]	Henon C, Vibert J, Eychenne T, Gruel N, Colmet-Daage L, Ngo C, et al. Single-cell multiomics profiling reveals heterogeneous transcriptional programs and microenvironment in DSRCTs. Cell Reports Med. 2024; 5(6): 101582.

[10]	Koelsche C, Schrimpf D, Stichel D, Sill M, Sahm F, Reuss DE, et al. Sarcoma classification by DNA methylation profiling. Nat Commun. 2021; 12(1): 498.