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
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.
