PT  - JOURNAL ARTICLE
AU  - Rao, Uma
AU  - Schoedel, Karen Elizabeth
AU  - Petrosko, Patricia
AU  - Sakai, Nozomi
AU  - LaFramboise, William
TI  - Genetic variants and copy number changes in soft tissue leiomyosarcoma detected by targeted amplicon sequencing
AID  - 10.1136/jclinpath-2019-205998
DP  - 2019 Dec 01
TA  - Journal of Clinical Pathology
PG  - 810--816
VI  - 72
IP  - 12
4099  - http://jcp.bmj.com/content/72/12/810.short
4100  - http://jcp.bmj.com/content/72/12/810.full
SO  - J Clin Pathol2019 Dec 01; 72
AB  - 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.