Complete loss of TP53 and RB1 is associated with complex genome and low immune infiltrate in pleomorphic rhabdomyosarcoma

Hannah C. Beird; Chia-Chin Wu; Michael Nakazawa; Davis Ingram; Joseph R. Daniele; Rossana Lazcano; Latasha Little; Christopher Davies; Najat C. Daw; Khalida Wani; Wei-Lien Wang; Xingzhi Song; Curtis Gumbs; Jianhua Zhang; Brian Rubin; Anthony Conley; Adrienne M. Flanagan; Alexander J. Lazar; P. Andrew Futreal

HGG Advances (Oct 2023)

Complete loss of TP53 and RB1 is associated with complex genome and low immune infiltrate in pleomorphic rhabdomyosarcoma

Hannah C. Beird,
Chia-Chin Wu,
Michael Nakazawa,
Davis Ingram,
Joseph R. Daniele,
Rossana Lazcano,
Latasha Little,
Christopher Davies,
Najat C. Daw,
Khalida Wani,
Wei-Lien Wang,
Xingzhi Song,
Curtis Gumbs,
Jianhua Zhang,
Brian Rubin,
Anthony Conley,
Adrienne M. Flanagan,
Alexander J. Lazar,
P. Andrew Futreal

Affiliations

Hannah C. Beird: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Corresponding author
Chia-Chin Wu: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Michael Nakazawa: Department of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Davis Ingram: Department of Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Joseph R. Daniele: TRACTION Platform, Division of Therapeutics Discovery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Rossana Lazcano: Department of Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Latasha Little: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Christopher Davies: Research Department of Pathology, UCL Cancer Institute, London WC1E 6DD, UK
Najat C. Daw: Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Khalida Wani: Department of Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Wei-Lien Wang: Department of Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Xingzhi Song: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Curtis Gumbs: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Jianhua Zhang: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Brian Rubin: Institute Chair, Cleveland Clinic, Cleveland, OH 44195, USA
Anthony Conley: Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Adrienne M. Flanagan: Research Department of Pathology, UCL Cancer Institute, London WC1E 6DD, UK; Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex HA7 4LP, UK
Alexander J. Lazar: Department of Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
P. Andrew Futreal: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

Journal volume & issue: Vol. 4, no. 4
p. 100224

Abstract

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Summary: Rhabdomyosarcoma accounts for roughly 1% of adult sarcomas, with pleomorphic rhabdomyosarcoma (PRMS) as the most common subtype. Survival outcomes remain poor for patients with PRMS, and little is known about the molecular drivers of this disease. To better characterize PRMS, we performed a broad array of genomic and immunostaining analyses on 25 patient samples. In terms of gene expression and methylation, PRMS clustered more closely with other complex karyotype sarcomas than with pediatric alveolar and embryonal rhabdomyosarcoma. Immune infiltrate levels in PRMS were among the highest observed in multiple sarcoma types and contrasted with low levels in other rhabdomyosarcoma subtypes. Lower immune infiltrate was associated with complete loss of both TP53 and RB1. This comprehensive characterization of the genetic, epigenetic, and immune landscape of PRMS provides a roadmap for improved prognostications and therapeutic exploration.

Published in HGG Advances

ISSN: 2666-2477 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Biology (General): Genetics
Website: https://www.cell.com/hgg-advances/home

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