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

doi:10.1016/j.xhgg.2023.100224

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

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

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.

Original language	English (US)
Article number	100224
Journal	Human Genetics and Genomics Advances
Volume	4
Issue number	4
DOIs	https://doi.org/10.1016/j.xhgg.2023.100224
State	Published - Oct 12 2023

Keywords

Complex karyotype
Pleomorphic rhabdomyosarcoma
Rhabdomyosarcoma
Sarcoma
TP53

ASJC Scopus subject areas

Molecular Medicine
Genetics(clinical)

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10.1016/j.xhgg.2023.100224

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Beird, H. C., Wu, C. C., Nakazawa, M., Ingram, D., Daniele, J. R., Lazcano, R., Little, L., Davies, C., Daw, N. C., Wani, K., Wang, W. L., Song, X., Gumbs, C., Zhang, J., Rubin, B., Conley, A., Flanagan, A. M., Lazar, A. J., & Futreal, P. A. (2023). Complete loss of TP53 and RB1 is associated with complex genome and low immune infiltrate in pleomorphic rhabdomyosarcoma. Human Genetics and Genomics Advances, 4(4), Article 100224. https://doi.org/10.1016/j.xhgg.2023.100224

Beird, HC , Wu, CC , Nakazawa, M, Ingram, D, Daniele, JR , Lazcano, R, Little, L, Davies, C, Daw, NC, Wani, K, Wang, WL , Song, X, Gumbs, C, Zhang, J, Rubin, B, Conley, A, Flanagan, AM, Lazar, AJ & Futreal, PA 2023, 'Complete loss of TP53 and RB1 is associated with complex genome and low immune infiltrate in pleomorphic rhabdomyosarcoma', Human Genetics and Genomics Advances, vol. 4, no. 4, 100224. https://doi.org/10.1016/j.xhgg.2023.100224

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

abstract = "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.",

keywords = "Complex karyotype, Pleomorphic rhabdomyosarcoma, Rhabdomyosarcoma, Sarcoma, TP53",

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

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AU - Beird, Hannah C.

AU - Wu, Chia Chin

AU - Nakazawa, Michael

AU - Ingram, Davis

AU - Daniele, Joseph R.

AU - Lazcano, Rossana

AU - Little, Latasha

AU - Davies, Christopher

AU - Daw, Najat C.

AU - Wani, Khalida

AU - Wang, Wei Lien

AU - Song, Xingzhi

AU - Gumbs, Curtis

AU - Zhang, Jianhua

AU - Rubin, Brian

AU - Conley, Anthony

AU - Flanagan, Adrienne M.

AU - Lazar, Alexander J.

AU - Futreal, P. Andrew

PY - 2023/10/12

Y1 - 2023/10/12

N2 - 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.

AB - 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.

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

Abstract

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