Department of Musculoskeletal Cancer Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China.
Cancer Genomics Proteomics. 2019 May-Jun;16(3):221-228. doi: 10.21873/cgp.20127.
BACKGROUND/AIM: Undifferentiated pleomorphic sarcomas (UPSs) are difficult to treat, with a high recurrence rate. However, the genetic and molecular characterization of recurrent UPS has not been identified.
In this study, we investigated the pathogenic and targetable genetic alterations in 16 paired locally pre-recurrent and post-recurrent UPS cases by targeted next-generation sequencing (466 genes).
Sequence variations were most frequently found in TP53 (66%), ATRX (34%), and RB1 (28%). In addition, for the first time, recurrent IL7R gene amplification (19%) and KMT2C gene mutation (16%) were detected in UPS. Interestingly, genetic alterations varied with tumor relapse. Importantly, targetable driver variants were found in recurrent UPS. Mutated genes were correlated with the cell cycle, PI3K/mTOR and RAS/MAPK signaling pathways. TMB was also found to be increased after tumor recurrence (4.6 vs. 7.5 mutations/MB, p=0.0343).
Routine use of targeted next-generation sequencing for recurrent UPS can facilitate timely therapeutic decision-making.
背景/目的：未分化多形性肉瘤（UPS）治疗困难，复发率高。然而，尚未确定复发性 UPS 的遗传和分子特征。
本研究通过靶向下一代测序（466 个基因），对 16 对局部预复发和复发后的 UPS 病例进行了致病性和可靶向的遗传改变分析。
序列变异最常见于 TP53（66%）、ATRX（34%）和 RB1（28%）。此外，首次在 UPS 中检测到复发性 IL7R 基因扩增（19%）和 KMT2C 基因突变（16%）。有趣的是，遗传改变随肿瘤复发而变化。重要的是，复发性 UPS 中存在可靶向的驱动变异。突变基因与细胞周期、PI3K/mTOR 和 RAS/MAPK 信号通路相关。肿瘤复发后 TMB 也增加（4.6 与 7.5 个突变/MB，p=0.0343）。
常规对复发性 UPS 进行靶向下一代测序有助于及时做出治疗决策。
