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

Naofumi Asano, Akihiko Yoshida, Sachiyo Mitani, Eisuke Kobayashi, Bunsyo Shiotani, Motokiyo Komiyama, Hiroyuki Fujimoto, Hirokazu Chuman, Hideo Morioka, Morio Matsumoto, Masaya Nakamura, Takashi Kubo, Mamoru Kato, Takashi Kohno, Akira Kawai, Tadashi Kondo, Hitoshi Ichikawa

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15 Citations (Scopus)

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 cancerrelated 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.

Original languageEnglish
Pages (from-to)12941-12952
Number of pages12
JournalOncotarget
Volume8
Issue number8
DOIs
Publication statusPublished - 2017 Jan 1

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Keywords

  • Dedifferentiated liposarcoma
  • Liposarcoma
  • Next-generation sequencing
  • Receptor tyrosine kinase
  • Well-differentiated liposarcoma

ASJC Scopus subject areas

  • Oncology

Cite this

Asano, N., Yoshida, A., Mitani, S., Kobayashi, E., Shiotani, B., Komiyama, M., Fujimoto, H., Chuman, H., Morioka, H., Matsumoto, M., Nakamura, M., Kubo, T., Kato, M., Kohno, T., Kawai, A., Kondo, T., & Ichikawa, H. (2017). Frequent amplification of receptor tyrosine kinase genes in welldifferentiated/ dedifferentiated liposarcoma. Oncotarget, 8(8), 12941-12952. https://doi.org/10.18632/oncotarget.14652