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

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.

Automated summary

Leiomyosarcoma (LMS) is a rare, aggressive mesenchymal tumor associated with genomic alterations, particularly in BRCA2. However, unlike carcinomas, there is no overlap with previously published gLOH-associated genes in LMS. Early stage LMS tumors with high gLOH scores have a longer disease-free interval following resection. This suggests that gLOH-LMS is driven by different genomic signals.