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J Pathol. 2016 Jan;238(1):63-73. doi: 10.1002/path.4636. Epub 2015 Oct 19.

The genomic landscape of epithelioid sarcoma cell lines and tumours.

Author information

Genetic Pathology Evaluation Centre, Vancouver, BC, Canada.
BC Cancer Research Centre, Vancouver, BC, Canada.
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Division of Orthopaedic Surgery, University of Toronto, ON, Canada.
Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada.
The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC, Canada.


We carried out whole genome and transcriptome sequencing on four tumour/normal pairs of epithelioid sarcoma. These index cases were supplemented with whole transcriptome sequencing of three additional tumours and three cell lines. Unlike rhabdoid tumour (the other major group of SMARCB1-negative cancers), epithelioid sarcoma shows a complex genome with a higher mutational rate, comparable to that of ovarian carcinoma. Despite this mutational burden, SMARCB1 mutations remain the most frequently recurring event and are probably critical drivers of tumour formation. Several cases show heterozygous SMARCB1 mutations without inactivation of the second allele, and we explore this further in vitro. Finding CDKN2A deletions in our discovery cohort, we evaluated CDKN2A protein expression in a tissue microarray. Six out of 16 cases had lost CDKN2A in greater than or equal to 90% of cells, while the remaining cases had retained the protein. Expression analysis of epithelioid sarcoma cell lines by transcriptome sequencing shows a unique profile that does not cluster with any particular tissue type or with other SWI/SNF-aberrant lines. Evaluation of the levels of members of the SWI/SNF complex other than SMARCB1 revealed that these proteins are expressed as part of a residual complex, similarly to previously studied rhabdoid tumour lines. This residual SWI/SNF is susceptible to synthetic lethality and may therefore indicate a therapeutic opportunity.


SMARCB1; epithelioid sarcoma; genomic landscape; next-generation sequencing

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