Molecular biomarkers for uterine leiomyosarcoma and endometrial stromal sarcoma

Uterine leiomyosarcoma (u-LMS) and endometrial stromal sarcoma (ESS) are among the most frequent soft tissue sarcomas, which, in adults, lead to fatal lung metastases and patients have an extremely poor prognosis. Due to their rarity and heterogeneity, there are no suitable biomarkers for diagnosis and prognosis, although some biomarker candidates have appeared. In 2017, The Cancer Genome Atlas (TCGA) Research Network's work on u-LMS has confirmed mutations and deletions in RB1, TP53 and PTEN. In addition, whole-exome sequencing of u-LMS has confirmed and demonstrated frequent alterations in TP53, RB1, α-thalassemia/mental retardation syndrome X-linked (ATRX) and mediator complex subunit 12 (MED12). MED12 is a useful biomarker to diagnose uterine-derived LMS and tumors arising from (LM) with a relatively favorable prognosis. TP53 and ATRX mutations can be important mechanisms in the pathogenesis of u-LMS and are correlated with a poor prognosis. In an update based on the 2014 WHO classification, low-grade ESS is often associated with gene rearrangement bringing about the JAZF 1-SUZ12 (formerly JAZF1-JJAZ1) fusion gene, whereas high-grade ESS is associated with the YWHAE-NUTM fusion gene. Low-grade ESS with JAZF1 rearrangement may correlate with metastasis. However, high-grade ESS with metastasis with YWHAE rearrangement shows a relatively favorable prognosis. The genetic/molecular genetic aberrations in u-LMS and ESS are reviewed, focusing on molecular biomarkers for these primary and metastatic tumors.