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Oncotarget. 2017 Feb 21;8(8):12941-12952. doi: 10.18632/oncotarget.14652.

Frequent amplification of receptor tyrosine kinase genes in welldifferentiated/ dedifferentiated liposarcoma.

Author information

1
Division of Rare Cancer Research, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
2
Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
3
Department of Pathology and Clinical Laboratory, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan.
4
Department of Clinical Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
5
Department of Musculoskeletal Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan.
6
Division of Genetics, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
7
Department of Urology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan.
8
Division of Translational Genomics, National Cancer Center-Exploratory Oncology Research and Clinical Trial Center, Chuo-ku, Tokyo 104-0045, Japan.
9
Department of Bioinformatics, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
10
Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.

Abstract

Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are closely related tumors commonly characterized by MDM2/CDK4 gene amplification, and lack clinically effective treatment options when inoperable. To identify novel therapeutic targets, we performed targeted genomic sequencing analysis of 19 WDLPS and 37 DDLPS tumor samples using a panel of 104 cancer-related genes (NCC oncopanel v3) developed specifically for genomic testing to select suitable molecular targeted therapies. The results of this analysis indicated that these sarcomas had very few gene mutations and a high frequency of amplifications of not only MDM2 and CDK4 but also other genes. Potential driver mutations were found in only six (11%) samples; however, gene amplification events (other than MDM2 and CDK4 amplification) were identified in 30 (54%) samples. Receptor tyrosine kinase (RTK) genes in particular were amplified in 18 (32%) samples. In addition, growth of a WDLPS cell line with IGF1R amplification was suppressed by simultaneous inhibition of CDK4 and IGF1R, using palbociclib and NVP-AEW541, respectively. Combination therapy with CDK4 and RTK inhibitors may be an effective therapeutic option for WDLPS/DDLPS patients with RTK gene amplification.

KEYWORDS:

dedifferentiated liposarcoma; liposarcoma; next-generation sequencing; receptor tyrosine kinase; well-differentiated liposarcoma

PMID:
28099935
PMCID:
PMC5355068
DOI:
10.18632/oncotarget.14652
[Indexed for MEDLINE]
Free PMC Article

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