Kim Yoon-Seob, Shin Sun, Jung Seung-Hyun, Chung Yeun-Jun
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
BMC Med Genet. 2020 Oct 12;21(1):200. doi: 10.1186/s12881-020-01137-4.
Dedifferentiated liposarcoma (DDLPS), which accounts for an estimated 15-20% of liposarcomas, is a high-grade and aggressive malignant neoplasm, exhibiting a poor response to available therapeutic agents. However, genetic alteration profiles of DDLPS as well as the role of NF1 mutations have not been studied extensively.
The current study reports a patient presenting with rapidly growing DDLPS accompanied by multiple lung and pleural metastases, in whom whole-exome sequencing revealed a NF1 truncating mutation of the known pathogenic variant, c.C7486T, p.R2496X, as well as multiple copy number alterations (CNAs), including the well-known 12q13-15 amplification, and multiple chromothripsis events encompassing potential cancer-related genes.
Our results suggest that, in addition to the 12q13-15 amplification, NF1 inactivation mutation and other CNAs may contribute to DDLPS tumorigenesis accompanied by aggressive clinical features.
去分化脂肪肉瘤（DDLPS）约占脂肪肉瘤的15%-20%，是一种高级别侵袭性恶性肿瘤，对现有治疗药物反应不佳。然而，DDLPS的基因改变谱以及NF1突变的作用尚未得到广泛研究。
本研究报告了一名患者，患有快速生长的DDLPS并伴有多处肺和胸膜转移，全外显子测序显示其存在已知致病变体c.C7486T、p.R2496X的NF1截短突变，以及多种拷贝数改变（CNA），包括众所周知的12q13-15扩增，以及多个涉及潜在癌症相关基因的染色体碎裂事件。
我们的结果表明，除了12q13-15扩增外，NF1失活突变和其他CNA可能导致伴有侵袭性临床特征的DDLPS肿瘤发生。
