Data from Genomic Evolutionary Patterns of Leiomyosarcoma and Liposarcoma
Year: 2023
Type: other
Abstract: Purpose: Leiomyosarcoma and liposarcoma are common subtypes of soft tissue sarcoma (STS). Patients with metastatic leiomyosarcoma or dedifferentiated liposarcoma (DDLPS) typically have worse outcomes compared with localized leiomyosarcoma or well-differentiated liposarcoma (WDLPS). A better understanding of genetic changes between primary/metastatic leiomyosarcoma and between WDLPS/DDLPS may provide insight into their genetic evolution. Experimental Design: We interrogated whole-exome sequencing (WES) from “trios” of normal tissue, primary tumor, and metastatic tumor from individual patients with leiomyosarcoma (n = 9), and trios of normal tissue, well-differentiated tumor, and dedifferentiated tumor from individual patients with liposarcoma (n = 19). Specifically, we performed mutational, copy number, and tumor evolution analyses on these cohorts and compared patterns among leiomyosarcoma and liposarcoma trios. Results: Leiomyosarcoma cases harbored shared drivers through a typical parent/child relationship where the metastatic tumor was derived from the primary tumor. In contrast, while all liposarcoma cases shared the characteristic focal chromosome 12 amplicon, most paired liposarcoma cases did not share additional mutations, suggesting a divergent evolutionary pattern from a common precursor. No highly recurrent genomic alterations from WES were identified that could be implicated as driving the progression of disease in either sarcoma subtype. Conclusions: From a genomic perspective, leiomyosarcoma metastases contain genetic alterations that are also found in primary tumors. WDLPS and DDLPS, however, appear to divergently evolve from a common precursor harboring 12q amplification, rather than as a transformation to a higher-grade tumor. Further efforts to identify specific drivers of these distinct evolutionary patterns may inform future translational and clinical research in STS.
Authors: Ali Amin-Mansour, Suzanne George, Stefano Sioletic, Scott L. Carter, Mara Rosenberg, Amaro Taylor-Weiner, Chip Stewart, Aaron Chevalier, Sara Seepo, Adam Tracy, Gad Getz, Jason L. Hornick, Marisa R. Nucci, Bradley Quade, George D. Demetri, Chandrajit P. Raut, Levi A. Garraway, Eliezer M. Van Allen, Andrew J. Wagner
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4361959441