Integrative Molecular Profiling in Leiomyosarcoma

ABSTRACT: Leiomyosarcoma (LMS) is a soft tissue tumor with a significant degree of morphologic and molecular heterogeneity. We employed integrative molecular profiling to discover and characterize molecular subtypes of LMS. Gene expression profiling was performed on 51 LMS samples. Unsupervised clustering demonstrated 3 reproducible LMS clusters. Array comparative genomic hybridization (aCGH) was performed on 20 LMS samples and demonstrated that the molecular subtypes defined by gene-expression showed distinct genomic changes. Tumors from the "muscle-enriched" cluster showed significantly increased copy number changes (p=0.04). Most muscle-enriched cases showed loss at 16q24 which contains FANCA, known to play an important role in DNA repair, and loss at 1p36 which contains PRDM16, whose loss promotes muscle differentiation. Immunohistochemistry was performed on LMS tissue microarrays (n= 377) for five markers with high levels of mRNA in the muscle-enriched cluster (ACTG2, CASQ2, SLMAP,CFL2, MYLK) and demonstrated significantly correlated expression of the 5 proteins (all pairwise p < 0.005). Expression of the 5 markers was associated with improved disease-specific survival (DSS) in a multivariate Cox regression analysis (p < 0.04). In this analysis that combined gene expression profiling, aCGH and immunohistochemistry, we characterized distinct molecular LMS subtypes, provided insight into their pathogenesis, and identified prognostic biomarkers. This set contains microarray slides from expression studies. VARIABLES: Phenotype: Tumour morphology Age: age at the time of the primary lesion diagnosis (*:Age of diagnosis at the time of tumor resection) Individual Compound Based Treatment: Patient received treatment (CT: exposure to chemotherapy, RT: exposure to radiation therapy) Organism Part: Primary tumour site (UT: uterine origin, ST: soft tissue origin; **:clinically most likely anatomic origin of the tumor) Disease State: Tumour status (P: primary tumor, M: metastatic tumor, LR: local recurrence, N/A: information not available.) Sex/Mating type: M(ale)/F(emale) Experiment type: aCGH or Expression type II

ORGANISM(S): Homo sapiens

PROVIDER: GSE17555 | GEO | 2009/11/12

SECONDARY ACCESSION(S): PRJNA118653

REPOSITORIES: GEO