Drivers of genomic loss of heterozygosity in leiomyosarcoma are distinct from carcinomas

Nathan D Seligson; Joy Tang; Dexter X Jin; Monica P Bennett; Julia A Elvin; Kiley Graim; John L Hays; Sherri Z Millis; Wayne O Miles; James L Chen

doi:10.1038/s41698-022-00271-x

Drivers of genomic loss of heterozygosity in leiomyosarcoma are distinct from carcinomas

NPJ Precis Oncol. 2022 Apr 25;6(1):29. doi: 10.1038/s41698-022-00271-x.

Authors

Nathan D Seligson^{1

2

3}, Joy Tang³, Dexter X Jin⁴, Monica P Bennett¹, Julia A Elvin⁴, Kiley Graim⁵, John L Hays^{3

6}, Sherri Z Millis⁴, Wayne O Miles⁷, James L Chen^{8

9}

Affiliations

¹ Department of Pharmacotherapy and Translational Research, The University of Florida, Jacksonville, FL, USA.
² Department of Pharmacogenomics and Translational Research, Nemours Children's Specialty Care, Jacksonville, FL, USA.
³ Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
⁴ Foundation Medicine Inc, Cambridge, MA, USA.
⁵ Department of Computer and Information Science and Engineering, The University of Florida, Gainesville, FL, USA.
⁶ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University, Columbus, OH, USA.
⁷ Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.
⁸ Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA. James.Chen@osumc.edu.
⁹ Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA. James.Chen@osumc.edu.

Abstract

Leiomyosarcoma (LMS) is a rare, aggressive, mesenchymal tumor. Subsets of LMS have been identified to harbor genomic alterations associated with homologous recombination deficiency (HRD); particularly alterations in BRCA2. Whereas genomic loss of heterozygosity (gLOH) has been used as a surrogate marker of HRD in other solid tumors, the prognostic or clinical value of gLOH in LMS (gLOH-LMS) remains poorly defined. We explore the genomic drivers associated with gLOH-LMS and their clinical import. Although the distribution of gLOH-LMS scores are similar to that of carcinomas, outside of BRCA2, there was no overlap with previously published gLOH-associated genes from studies in carcinomas. We note that early stage tumors with elevated gLOH demonstrated a longer disease-free interval following resection in LMS patients. Taken together, and despite similarities to carcinomas in gLOH distribution and clinical import, gLOH-LMS are driven by different genomic signals. Additional studies will be required to isolate and confirm the unique differences in biological factors driving these differences.

Abstract

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