Spectrum of mutations in leiomyosarcomas identified by clinical targeted next-generation sequencing

Paul J. Lee, Naomi S. Yoo, Ian S. Hagemann, John D. Pfeifer, Catherine E. Cottrell, Haley J. Abel, Eric J. Duncavage

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33 Scopus citations


Recurrent genomic mutations in uterine and non-uterine leiomyosarcomas have not been well established. Using a next generation sequencing (NGS) panel of common cancer-associated genes, 25 leiomyosarcomas arising from multiple sites were examined to explore genetic alterations, including single nucleotide variants (SNV), small insertions/deletions (indels), and copy number alterations (CNA). Sequencing showed 86 non-synonymous, coding region somatic variants within 151 gene targets in 21 cases, with a mean of 4.1 variants per case; 4 cases had no putative mutations in the panel of genes assayed. The most frequently altered genes were TP53 (36%), ATM and ATRX (16%), and EGFR and RB1 (12%). CNA were identified in 85% of cases, with the most frequent copy number losses observed in chromosomes 10 and 13 including PTEN and RB1; the most frequent gains were seen in chromosomes 7 and 17. Our data show that deletions in canonical cancer-related genes are common in leiomyosarcomas. Further, the spectrum of gene mutations observed shows that defects in DNA repair and chromosomal maintenance are central to the biology of leiomyosarcomas, and that activating mutations observed in other common cancer types are rare in leiomyosarcomas.

Original languageEnglish
Pages (from-to)156-161
Number of pages6
JournalExperimental and Molecular Pathology
Issue number1
StatePublished - Feb 1 2017


  • Copy number alterations
  • DNA mutational analysis
  • DNA sequencing
  • Deep sequencing
  • Leiomyosarcoma
  • Molecular diagnostics
  • Single nucleotide variant


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