Clinically relevant molecular subtypes in leiomyosarcoma
A partir d'échantillons tumoraux prélevés sur 99 patients atteints d'un léiomyosarcome, puis validée sur des données complémentaires portant sur 82 patients inclus dans le projet "The Cancer genome Atlas", cette étude met en évidence trois sous-types moléculaires de la maladie
Purpose: Leiomyosarcoma (LMS) is a malignant neoplasm with smooth muscle differentiation. Little is known about its molecular heterogeneity and no targeted therapy currently exists for LMS. Recognition of different molecular subtypes is necessary to evaluate novel therapeutic options. In a previous study on 51 LMS, we identified three molecular subtypes in LMS. The current study was performed to determine whether the existence of these subtypes could be confirmed in independent cohorts.
Experimental Design: 99 cases of LMS were expression profiled with 3'end RNA-Sequencing (3SEQ). Consensus Clustering was conducted to determine the optimal number of subtypes.
Results: We identified 3 LMS molecular subtypes and confirmed this finding by analyzing publically available data on 82 LMS from The Cancer Genome Atlas (TCGA). We identified two new FFPE tissue-compatible diagnostic immunohistochemical markers; LMOD1 for subtype I LMS and ARL4C for subtype II LMS. An LMS tissue microarray with known clinical outcome was used to show that subtype I LMS is associated with good outcome in extrauterine LMS while subtype II LMS is associated with poor prognosis in both uterine and extrauterine LMS. The LMS subtypes showed significant differences in expression levels for genes for which novel targeted therapies are being developed, suggesting that LMS subtypes may respond differentially to these targeted therapies.
Conclusions: We confirm the existence of 3 molecular subtypes in LMS using two independent datasets and show that the different molecular subtypes are associated with distinct clinical outcomes. The findings offer an opportunity for treating LMS in a subtype-specific targeted approach.
Clinical Cancer Research , article en libre accès, 2015