Abstract B05: Myxoid liposarcoma: A molecular and clinicopathological analysis by targeted next-generation sequencing and fluorescence in situ hybridization
Authors: Trautmann Marcel , Krüger Arne , Jeiler Birte , Bertling Christian , Menzel Jasmin , Cyra Magdalene , Steinestel Konrad , Grünewald Inga , Åman Pierre , Wardelmann Eva , Huss Sebastian , Hartmann Wolfgang 
Published: December 2017

Abstract
Introduction: Myxoid liposarcoma (MLS) is the second most common type of liposarcoma, accounting for 30-35% of all LS cases. Over 90% of tumors are characterized by a reciprocal translocation t (12; 16) (q13; p11), resulting in a pathogenic gene fusion. The chimeric FUS-DDIT3 fusion protein is suggested to play a crucial role in MLS tumorigenesis and progression, although the specific biological function and the mechanism of action remain to be defined. We compiled a comprehensive cohort of 105 well-characterized MLS tissue specimens to identify actionable genetic aberrations.
Methods: Targeted next-generation sequencing (NGS) using the Illumina MiSeq platform was performed to examine the mutational status of 23 cancer-related genes (covering all exons) known to be frequently mutated across various neoplasms. Furthermore, we examined the amplification/deletion status and characterized the specific chromosomal FUS-DDIT3 rearrangements by FISH and RT-PCR. A multivariate analysis was conducted to investigate the prognostic significance of mutation/amplification/deletion status.
Results: Targeted next-generation sequencing drives the potential to generate comprehensive genetic information including less frequent mutated genes relevant for actionable treatments and prognostic assessment. Besides PIK3CA, six additional genes showed at least five mutations, including AKT1, CTNNB1, EGFR, ERBB2, MET and PTEN. Several oncogenic mutations were detected which have not been reported in MLS previously. We demonstrated several gene amplification/deletion events in MLS.
Conclusion: Our results indicate the occurrence of mutational aberrations besides the chromosomal FUS-DDIT3 hallmark. These appear not to be related to specific subtypes of FUS-DDIT3 fusion transcripts in terms of a molecular pattern. Molecular screening for actionable mutations might represent a rational tool for the implementation of innovative targeted therapeutic approaches in MLS. To our best knowledge, this study is the most extensive one to yield a detailed map of actionable genetic aberrations across a comprehensive cohort of &gt;100 well-characterized MLS tissue specimens. Moreover, it reveals several molecular alteration-specific targets for innovative therapy strategies.
Citation Format: Marcel Trautmann, Arne Krüger, Birte Jeiler, Christian Bertling, Jasmin Menzel, Magdalene Cyra, Konrad Steinestel, Inga Grünewald, Pierre Åman, Eva Wardelmann, Sebastian Huss, Wolfgang Hartmann. Myxoid liposarcoma: A molecular and clinicopathological analysis by targeted next-generation sequencing and fluorescence in situ hybridization [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B05.