Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY 10065, USA.
Genes Chromosomes Cancer. 2013 Jun;52(6):538-50. doi: 10.1002/gcc.22050. Epub 2013 Mar 5.
Spindle cell rhabdomyosarcoma (RMS) is a rare form of RMS with different clinical characteristics between children and adult patients. Its genetic hallmark remains unknown and it remains debatable if there is pathogenetic relationship between the spindle cell and the so-called sclerosing RMS. We studied two pediatric and one adult spindle cell RMS by next generation RNA sequencing and FusionSeq data analysis to detect novel fusions. An SRF-NCOA2 fusion was detected in a spindle cell RMS from the posterior neck in a 7-month-old child. The fusion matched the tumor karyotype and was confirmed by FISH and RT-PCR, which showed fusion of SRF exon 6 to NCOA2 exon 12. Additional 14 spindle cell (from 8 children and 6 adults) and 4 sclerosing (from 2 children and 2 adults) RMS were tested by FISH for the presence of abnormalities in NCOA2, SRF, as well as for PAX3 and NCOA1. NCOA2 rearrangements were found in two additional spindle cell RMS from a 3-month-old and a 4-week-old child. In the latter tumor, TEAD1 was identified by rapid amplification of cDNA ends (RACE) to be the NCOA2 gene fusion partner. None of the adult tumors were positive for NCOA2 rearrangement. Despite similar histomorphology in adults and young children, these results suggest that spindle cell RMS is a heterogeneous disease genetically as well as clinically. Our findings also support a relationship between NCOA2-rearranged spindle cell RMS occurring in young childhood and the so-called congenital RMS, which often displays rearrangements at 8q13 locus (NCOA2).
梭形细胞横纹肌肉瘤（RMS）是一种罕见的 RMS 形式，儿童和成年患者的临床特征不同。其遗传特征尚不清楚，关于梭形细胞与所谓的硬化型 RMS 是否存在发病机制关系仍存在争议。我们通过下一代 RNA 测序和 FusionSeq 数据分析研究了两例儿科和一例成人梭形细胞 RMS，以检测新的融合。在一个 7 个月大的儿童后颈部的梭形细胞 RMS 中检测到 SRF-NCOA2 融合。该融合与肿瘤核型匹配，并通过 FISH 和 RT-PCR 证实，显示 SRF 外显子 6 与 NCOA2 外显子 12 融合。还通过 FISH 检测了另外 14 例梭形细胞（来自 8 名儿童和 6 名成人）和 4 例硬化型 RMS（来自 2 名儿童和 2 名成人）中 NCOA2、SRF 以及 PAX3 和 NCOA1 是否存在异常。在另外 2 例来自 3 个月大和 4 周大的儿童的梭形细胞 RMS 中发现了 NCOA2 重排。在后一种肿瘤中，通过快速扩增 cDNA 末端（RACE）鉴定出 TEAD1 是 NCOA2 基因融合伙伴。没有一例成人肿瘤 NCOA2 重排阳性。尽管成年人和幼儿的组织形态学相似，但这些结果表明梭形细胞 RMS 在遗传和临床方面都是一种异质性疾病。我们的研究结果还支持了在幼儿中发生的 NCOA2 重排梭形细胞 RMS 与所谓的先天性 RMS 之间的关系，后者通常在 8q13 位点（NCOA2）显示重排。
