Li Chengfang, Shen Yaoyuan, Ren Yan, Liu Wei, Li Man, Liang Weihua, Liu Chunxia, Li Feng
Department of Pathology, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, China; Department of Pathology, The Affiliated Hospital of Zun Yi Medical College, Zunyi, Guizhou 563000, China.
Department of Pathology, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, China.
Hum Pathol. 2016 Sep;55:143-50. doi: 10.1016/j.humpath.2016.05.006. Epub 2016 May 27.
Liposarcoma (LPS) is one of the most prevalent soft tissue sarcomas. LPS shows a poor response to radiation and chemotherapy. The causes of death in patients with LPS include locally recurrent and metastatic disease. We sought to examine novel gene mutations and pathways in primary and matched recurrent LPSs to identify potential therapeutic targets. We conducted a high-throughput analysis of 238 known mutations in 19 oncogenes using Sequenom MassARRAY technology. Nucleic acids were extracted from 19 primary and recurrent LPS samples, encompassing 9 dedifferentiated LPSs (DDLPS), 9 myxoid/round cell LPSs, and 1 pleomorphic LPS. Mutation screening revealed missense mutations in 21.1% (4/19) of the LPS specimens, including 4 different genes (FGFR1, FGFR3, PIK3CA, and KIT). Based on histologic subtypes, 22.2% DDLPS (2/9) and 22.2% myxoid cell LPS (2/9) contained gene mutations. Specifically, 3 (23.1%) of 13 primary tumors harbored mutations. Furthermore, although gene mutations were identified in 1 (11.1%) of 9 recurrent LPS samples, the difference between the primary and the recurrence was not statistically significant. Analysis of patient survival data indicated that patients harboring FGFR1/3 mutations experienced reduced overall survival (P<.05). Despite the limited number of samples, our findings provide the first evidence of FGFR1/3 mutations in DDLPS, which were associated with poor clinical outcomes. The FGFR pathway may play an important role in the development and progression of DDLPS and warrants further investigation; moreover, PIK3CA mutation is a common event (11.1%) in myxoid cell LPS.
脂肪肉瘤（LPS）是最常见的软组织肉瘤之一。LPS对放疗和化疗反应不佳。LPS患者的死亡原因包括局部复发和转移性疾病。我们试图研究原发性和配对复发性LPS中的新基因突变和信号通路，以确定潜在的治疗靶点。我们使用Sequenom MassARRAY技术对19个癌基因中的238个已知突变进行了高通量分析。从19个原发性和复发性LPS样本中提取核酸，包括9个去分化脂肪肉瘤（DDLPS）、9个黏液样/圆形细胞脂肪肉瘤和1个多形性脂肪肉瘤。突变筛查显示，21.1%（4/19）的LPS标本存在错义突变，包括4个不同基因（FGFR1、FGFR3、PIK3CA和KIT）。根据组织学亚型，22.2%的DDLPS（2/9）和22.2%的黏液样细胞脂肪肉瘤（2/9）含有基因突变。具体而言，13个原发性肿瘤中有3个（23.1%）存在突变。此外，虽然在9个复发性LPS样本中有1个（约11.1%）发现了基因突变，但原发性和复发性之间的差异无统计学意义。患者生存数据分析表明，携带FGFR1/3突变的患者总生存期缩短（P<0.05）。尽管样本数量有限，但我们的研究结果首次证明了DDLPS中存在FGFR1/3突变，这与不良临床结果相关。FGFR信号通路可能在DDLPS的发生和发展中起重要作用，值得进一步研究；此外，PIK3CA突变在黏液样细胞脂肪肉瘤中是常见事件（11.1%）。
