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

IF 3.3 Q2 GENETICS & HEREDITY

HGG Advances Pub Date : 2023-07-19 eCollection Date: 2023-10-12 DOI:10.1016/j.xhgg.2023.100224

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

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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.

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多形性横纹肌肉瘤中TP53和RB1的完全缺失与复杂基因组和低免疫浸润有关。

横纹肌肉瘤约占成人肉瘤的1%，多形性横纹肌肉瘤（PRMS）是最常见的亚型。PRMS患者的生存结果仍然很差，对这种疾病的分子驱动因素知之甚少。为了更好地表征PRMS，我们对25个患者样本进行了广泛的基因组和免疫染色分析。在基因表达和甲基化方面，PRMS与其他复杂核型肉瘤的聚集性比与儿童肺泡和胚胎性横纹肌肉瘤的聚集更紧密。在多种肉瘤类型中，PRMS的免疫浸润水平最高，而在其他横纹肌肉瘤亚型中，免疫浸润水平较低。较低的免疫浸润与TP53和RB1的完全丧失有关。PRMS的遗传、表观遗传学和免疫景观的全面表征为改善预后和治疗探索提供了路线图。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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