Abstract 401: Gene expression signatures differentiate primary and metastatic uterine leiomyosarcoma.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Leiomyosarcoma (LMS) is the most common uterine sarcoma, but is a rare cancer. The genetic events related to LMS metastasis are unknown to date. The aim of the present study was to compare the global gene expression patterns of primary uterine LMS and LMS metastases in order to identify potential biological targets. Gene expression profiles of 13 primary uterine LMS and 15 LMS metastases were analyzed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry. Unsupervised hierarchical clustering using all 54,675 genes in the array separated primary from metastatic LMS samples. We identified 203 unique probes that were significantly differentially expressed in the two tumor groups by greater than 2-fold with 1% FDR cutoff using one-way ANOVA with Benjamini-Hochberg correction, of which 94 and 109 were overexpressed in primary and metastatic LMS, respectively. Genes overexpressed in primary uterine LMS included OSTN, NLGN4X, NLGN1, SLITRK4, MASP1, XRN2, ASS1, RORB, HRASLS and TSPAN7. Genes overexpressed in LMS metastases included FOLR3, TDO2, CRYM, GJA1, TSPAN10, THBS1, SGK1, SHMT1, EGR2 and AGT. Results for selected genes were validated by quantitative real-time PCR and immunohistochemistry. We present the first study in which gene expression profiling was shown to distinguish between primary uterine LMS and LMS metastases. The molecular signatures unique to primary and metastatic LMS may aid in understanding tumor progression in this cancer and in providing a molecular basis for prognostic studies and therapeutic target discovery. Citation Format: Ben Davidson, Vera Maria Abeler, Mette Forsund, Arild Holth, Ie-Ming Shih, Gunnar B. Kristensen, Li Chen, Yanqin Yang, Tian-Li Wang. Gene expression signatures differentiate primary and metastatic uterine leiomyosarcoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 401. doi:10.1158/1538-7445.AM2013-401