Pathogenic NF1 truncating mutation and copy number alterations in a dedifferentiated liposarcoma with multiple lung meta
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CASE REPORT
Open Access
Pathogenic NF1 truncating mutation and copy number alterations in a dedifferentiated liposarcoma with multiple lung metastasis: a case report Yoon-Seob Kim1,2,3, Sun Shin1,2,3, Seung-Hyun Jung2,3,4 and Yeun-Jun Chung1,2,3,5*
Abstract Background: 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. Case presentation: 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 wellknown 12q13–15 amplification, and multiple chromothripsis events encompassing potential cancer-related genes. Conclusions: 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. Keywords: Case report, Copy number alternation, Liposarcoma, Mutation, NF1, Copy number alteration
Background Liposarcoma is the most common type of adult soft tissue sarcoma. Dedifferentiated liposarcoma (DDLPS), which accounts for an estimated 15–20% of liposarcomas, is a high-grade, aggressive disease that shows a poor response to available therapies [1]. Genetic analysis of DDLPS via The Cancer Genome Atlas (TCGA) project revealed that, compared with other solid tumors, DDLPS carried frequent copy number alterations (CNA) including recurrent amplification at 12q13–15, and relatively lower somatic mutations with only a few recurrently mutated genes, such as TP53 and ATRX [2]. Regarding CNAs, DDLPS is characterized by * Correspondence: [email protected] 1 Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea 2 Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Full list of author information is available at the end of the article
highly recurrent amplifications in the 12q13–15 region that contains the potential oncogenes, MDM2, CDK4, YEATS4, and FRS2, and the adipocytic differentiation factors, DDIT, PTPRQ, and HMGA2 [2–6]. In addition to the 12q13–15 amplification, other CNAs such as the gain of 1p32 (JUN), and the loss of 17q11 (NF1) and Xq21 (ATRX) have been identified in DDLPS [2–6]. However, genetic alteration profiles of DDLPS have not been studied extensively. According to studies such as GENIE [7] and TCGA [2], NF1 mutations in DDLPS are rare, being limited to 2/179 cases in GENIE and 1/56 cases in TCGA. (Fig. S1A). MDM4 amplification was observed in 0.6 and 5% of DDLPS cases via the GENIE study [7] and the TCGA study [2], respectively (Fig. S1A
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