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Genetic variants and copy number changes in soft tissue leiomyosarcoma detected by targeted amplicon sequencing
  1. Uma Rao1,
  2. Karen Elizabeth Schoedel2,
  3. Patricia Petrosko3,
  4. Nozomi Sakai2,
  5. William LaFramboise3
  1. 1Gynecologic Cancer Center of Excellence, Women's Health Integrated Research Center, Annandale, Virginia, USA
  2. 2Pathology, UPMC, Pittsburgh, Pennsylvania, USA
  3. 3Pathology, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA
  1. Correspondence to Dr Karen Elizabeth Schoedel,Pathology, UPMC, Pittsburgh, Pennsylvania, USA; schoedelke{at}


Aims Leiomyosarcomas (LMSs) occur in various tissues and harbour potential for metastases. The genomic landscape of LMS is poorly understood. In an effort to improve understanding of the LMS genome, we analysed 11 LMSs of somatic soft tissue including matching tissue of normal phenotype.

Methods DNA derived from microdissected tumour domains and matching normal tissue underwent amplicon sequencing of 409 tumour suppressors and oncogenes using the Ion Torrent Comprehensive Cancer Panel.

Results Genomic changes were heterogeneous with few recurrent abnormalities detected. Coding variants were identified in genes involved in signal transduction, transcriptional regulation and DNA repair. There were variants in several genes related to angiogenesis and GPR124 variants (TEM5) were confirmed by immunohistochemical analysis of a LMS tissue microarray. Surprisingly, there were shared coding variants in tumour and corresponding normal tissue.

Conclusions LMSs are a very heterogeneous population lacking recurrent somatic abnormalities. The presence of damaging mutations in normal tissue may reflect either a germline predisposition or field effect rather than tissue contamination. Hopeful therapeutic targets appear to be those related to AKT/MTOR pathway.

  • leiomyosarcoma
  • targeted amplicon sequencing
  • molecular pathology
  • genes
  • angiogenesis
  • copy number
  • mutation

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  • Handling editor Runjan Chetty.

  • Contributors All authors have contributed significantly to this work including design, laboratory work and/or manuscript preparation and approval.

  • Funding This project utilised the University of Pittsburgh Medical Center-Hillman Cancer Center shared resource facility (Cancer Genomics Facility) supported in part by award P30CA047904 (Dr R. Ferris).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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