完全丧失TP53和RB1与多形横纹肌肉瘤的复杂基因组和低免疫浸润相关。
Complete loss of TP53 and RB1 is associated with complex genome and low immune infiltrate in pleomorphic rhabdomyosarcoma.
发表日期：2023 Oct 12
作者：
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
来源：
Epigenetics & Chromatin
摘要：
横纹肌肉瘤（Rhabdomyosarcoma）占成人肉瘤的大约1％，其中以多形性横纹肌肉瘤（pleomorphic rhabdomyosarcoma, PRMS）最为常见。PRMS患者的生存结果仍然较差，对该疾病的分子驱动因素知之甚少。为了更好地描述PRMS，我们对25个病人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与其他复杂核型的肉瘤相比，与小儿泡型和胚胎型横纹肌肉瘤更为接近。PRMS中的免疫浸润水平在多种肉瘤类型中属于最高水平，并与其他横纹肌肉瘤亚型的低水平形成对比。较低的免疫浸润与TP53和RB1的完全缺失相关。对PRMS的基因、表观遗传和免疫景观的全面描述为改善预后和治疗探索提供了路线图。© 2023 The Authors.
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.© 2023 The Authors.