Please use this identifier to cite or link to this item:
https://doi.org/10.18632/oncotarget.6464
Title: | Genomic landscape of liposarcoma | Authors: | Kanojia, D Nagata, Y Garg, M Lee, D.H Sato, A Yoshida, K Sato, Y Sanada, M Mayakonda, A Bartenhagen, C Klein, H.-U Doan, N.B Said, J.W Mohith, S Gunasekar, S Shiraishi, Y Chiba, K Tanaka, H Miyano, S Myklebost, O Yang, H Dugas, M Meza-Zepeda, L.A Silberman, A.W Forscher, C Tyner, J.W Ogawa, S Phillip Koeffler, H |
Keywords: | ATM protein carboxypeptidase carboxypeptidase M checkpoint kinase 1 checkpoint kinase 2 cyclin dependent kinase 4 DNA epidermal growth factor receptor epidermal growth factor receptor 3 genomic DNA high mobility group A2 protein Janus kinase laminin alpha4 microRNA 15a microRNA 16 mitogen activated protein kinase neurofibromin protein MDM2 protein p53 somatomedin B somatomedin C receptor STAT protein transcription factor RUNX3 unclassified drug Wnt protein transcriptome apoptosis ARID1A gene Article ATM gene cancer genetics carcinogenesis CDK4 gene CHEK1 gene CHEK2 gene chromosome 11q chromosome 13q chromosome 1p controlled study copy number variation CPM gene DNA damage drug research ERBB3 gene FAT3 gene gene gene amplification gene deletion gene mutation genetic heterogeneity genetic procedures genome analysis HMGA2 gene human human cell human tissue IGF1R gene IGF2 gene in vitro study in vivo study LAMA4 gene liposarcoma major clinical study MDC1 gene MDM2 gene MIR15A gene MIR16 1 gene MIR557 gene molecularly targeted therapy MXRA5 gene NF1 gene oncogene PLEC gene polymerase chain reaction RUNX3 gene signal transduction single nucleotide polymorphism somatic mutation targeted exome sequencing TP53 gene tumor differentiation UAP1 gene whole exome sequencing animal DNA microarray dna mutational analysis flow cytometry gene silencing genetics high throughput sequencing liposarcoma mouse nonobese diabetic mouse SCID mouse soft tissue tumor xenograft Animals DNA Mutational Analysis Flow Cytometry Gene Knockdown Techniques Heterografts High-Throughput Nucleotide Sequencing Humans Liposarcoma Mice Mice, Inbred NOD Mice, SCID Oligonucleotide Array Sequence Analysis Polymerase Chain Reaction Polymorphism, Single Nucleotide Soft Tissue Neoplasms Transcriptome |
Issue Date: | 2015 | Publisher: | Impact Journals LLC | Citation: | Kanojia, D, Nagata, Y, Garg, M, Lee, D.H, Sato, A, Yoshida, K, Sato, Y, Sanada, M, Mayakonda, A, Bartenhagen, C, Klein, H.-U, Doan, N.B, Said, J.W, Mohith, S, Gunasekar, S, Shiraishi, Y, Chiba, K, Tanaka, H, Miyano, S, Myklebost, O, Yang, H, Dugas, M, Meza-Zepeda, L.A, Silberman, A.W, Forscher, C, Tyner, J.W, Ogawa, S, Phillip Koeffler, H (2015). Genomic landscape of liposarcoma. Oncotarget 6 (40) : 42429-42444. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.6464 | Abstract: | Liposarcoma (LPS) is the most common type of soft tissue sarcoma accounting for 20% of all adult sarcomas. Due to absence of clinically effective treatment options in inoperable situations and resistance to chemotherapeutics, a critical need exists to identify novel therapeutic targets. We analyzed LPS genomic landscape using SNP arrays, whole exome sequencing and targeted exome sequencing to uncover the genomic information for development of specific anti-cancer targets. SNP array analysis indicated known amplified genes (MDM2, CDK4, HMGA2) and important novel genes (UAP1, MIR557, LAMA4, CPM, IGF2, ERBB3, IGF1R). Carboxypeptidase M (CPM), recurrently amplified gene in well-differentiated/de-differentiated LPS was noted as a putative oncogene involved in the EGFR pathway. Notable deletions were found at chromosome 1p (RUNX3, ARID1A), chromosome 11q (ATM, CHEK1) and chromosome 13q14.2 (MIR15A, MIR16-1). Significantly and recurrently mutated genes (false discovery rate < 0.05) included PLEC (27%), MXRA5 (21%), FAT3 (24%), NF1 (20%), MDC1 (10%), TP53 (7%) and CHEK2 (6%). Further, in vitro and in vivo functional studies provided evidence for the tumor suppressor role for Neurofibromin 1 (NF1) gene in different subtypes of LPS. Pathway analysis of recurrent mutations demonstrated signaling through MAPK, JAK-STAT, Wnt, ErbB, axon guidance, apoptosis, DNA damage repair and cell cycle pathways were involved in liposarcomagenesis. Interestingly, we also found mutational and copy number heterogeneity within a primary LPS tumor signifying the importance of multi-region sequencing for cancer-genome guided therapy. In summary, these findings provide insight into the genomic complexity of LPS and highlight potential druggable pathways for targeted therapeutic approach. | Source Title: | Oncotarget | URI: | https://scholarbank.nus.edu.sg/handle/10635/175523 | ISSN: | 19492553 | DOI: | 10.18632/oncotarget.6464 |
Appears in Collections: | Staff Publications Elements |
Show full item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
10_18632_oncotarget_6464.pdf | 2.58 MB | Adobe PDF | OPEN | None | View/Download |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.