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

Naofumi Asano1,2, Akihiko Yoshida3, Sachiyo Mitani4

  • 1Division of Rare Cancer Research, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.

Oncotarget
|January 19, 2017
PubMed

Insights

Well-differentiated and dedifferentiated liposarcomas often have MDM2/CDK4 gene amplification. Combination therapy targeting CDK4 and receptor tyrosine kinases (RTKs) may offer new treatment options for these rare cancers.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are rare soft tissue sarcomas.
  • These tumors frequently exhibit MDM2/CDK4 gene amplification.
  • Current treatment options for inoperable WDLPS/DDLPS are limited.

Purpose of the Study:

  • To identify novel therapeutic targets in WDLPS and DDLPS.
  • To analyze the genomic landscape of these liposarcomas.
  • To explore potential combination therapies.

Main Methods:

  • Targeted genomic sequencing of 56 WDLPS/DDLPS tumor samples using the NCC oncopanel v3.
  • Analysis of gene mutations and amplifications.
  • In vitro study of a WDLPS cell line with IGF1R amplification.

Main Results:

  • Liposarcomas showed few mutations but frequent gene amplifications beyond MDM2/CDK4.
  • Receptor tyrosine kinase (RTK) genes were amplified in 32% of samples.
  • Simultaneous inhibition of CDK4 and IGF1R suppressed WDLPS cell growth.

Conclusions:

  • Gene amplifications, particularly in RTK genes, are common in WDLPS/DDLPS.
  • Combination therapy with CDK4 and RTK inhibitors shows promise for treating WDLPS/DDLPS with RTK amplification.
Keywords:
dedifferentiated liposarcomaliposarcomanext-generation sequencingreceptor tyrosine kinasewell-differentiated liposarcoma

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