Departments of Biopathology.
Claude Bernard University Lyon 1, INSERM 1052, CNRS 5286, Cancer Research Center of Lyon (CRCL), Lyon University, Lyon.
Am J Surg Pathol. 2020 May;44(5):607-616. doi: 10.1097/PAS.0000000000001464.
Rhabdomyosarcoma (RMS) encompasses a heterogenous collection of tumors in which new groups have recently been identified that improved the World Health Organization (WHO) classification. While performing RNA-sequencing in our routine practice, we identified 3 cases of well-differentiated RMS harboring new fusion genes. We also analyzed these tumors through array-comparative genomic hybridization. Clinically, these tumors were deep paraspinal tumors, occurring in neo-nat and young children. The patients underwent resection and adjuvant therapy. At the time of last follow-up (ranging from 12 to 108 mo), they were alive without disease. Histologically, these tumors consisted of well-differentiated rhabdomyoblastic proliferations with nuclear atypia, infiltrative borders, and a specific growth pattern. These tumors harbored new fusion genes involving SRF and either FOXO1 or NCOA1. We compared the expression profiles of these 3 tumors to the expression data of a series of 33 skeletal muscle tumors including embryonal RMSs, alveolar rhandomyosarcomas, RMSs with VGLL2 fusions, RMSs with the myoD1 mutation, EWSR1/FUS-TFCP2 epithelioid and spindle cell RMSs of the bone, and rhabdomyomas with PTCH1 loss. According to clustering analyses, the 3 SRF-fused tumors formed a distinct group with a specific expression profile different from that of the other types of skeletal muscle tumors. Array-comparative genomic hybridization showed a recurrent gain of chromosome 11. These 3 tumors define a new group of RMS associated with a fusion of the SRF gene. FOXO1 rearrangements, usually used to confirm the diagnosis of alveolar RMS and identify poor-outcome RMSs, were identified in a nonalveolar RMS for the first time.
横纹肌肉瘤（RMS）包含一组异质性肿瘤，其中最近又确定了一些新的肿瘤亚群，这些亚群改善了世界卫生组织（WHO）的分类。在我们的常规实践中进行 RNA 测序时，我们发现了 3 例具有新融合基因的分化良好的 RMS。我们还通过比较基因组杂交分析了这些肿瘤。临床上，这些肿瘤是深部脊柱旁肿瘤，发生在新生儿和幼儿中。患者接受了手术切除和辅助治疗。在最后一次随访时（范围从 12 到 108 个月），他们无病生存。组织学上，这些肿瘤由分化良好的横纹肌母细胞增生组成，具有核异型性、浸润性边界和特定的生长模式。这些肿瘤具有新的融合基因，涉及 SRF 和 FOXO1 或 NCOA1。我们将这 3 例肿瘤的表达谱与包括胚胎性 RMS、肺泡横纹肌肉瘤、具有 VGLL2 融合的 RMS、具有 myoD1 突变的 RMS、EWSR1/FUS-TFCP2 上皮样和梭形细胞 RMS 以及具有 PTCH1 缺失的横纹肌瘤在内的 33 例骨骼肌肿瘤的表达数据进行了比较。根据聚类分析，3 例 SRF 融合肿瘤形成了一个独特的组，具有与其他类型的骨骼肌肿瘤不同的特定表达谱。比较基因组杂交显示 11 号染色体经常出现增益。这 3 例肿瘤定义了一个与 SRF 基因融合相关的 RMS 新亚群。FOXO1 重排通常用于确认肺泡 RMS 的诊断并确定预后不良的 RMS，这是首次在非肺泡 RMS 中发现。
