title: Molecular subtyping of leiomyosarcoma with 3' end RNA sequencing.
abstract: 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. We performed expression profiling on 99 cases of LMS with 3'end RNA sequencing (3SEQ) and demonstrated the existence of 3 molecular subtypes in this cohort. We consequently showed that these molecular subtypes are reproducible using an independent cohort of 82 LMS cases from TCGA. Two new formalin-fixed, paraffin-embedded (FFPE) tissue-compatible diagnostic immunohistochemical markers were identified for two of the three subtypes: LMOD1 for subtype I LMS and ARL4C for subtype II LMS. Subtype I and subtype II LMS were associated with good and poor prognosis, respectively. Here, we describe the details of LMS diagnosis, RNA isolation, 3SEQ library construction, 3SEQ sequencing data analysis and molecular subtype determination. The 3SEQ data produced in this study was deposited into Gene Expression Omnibus (GEO) under GSE45510.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305 USA ; Department of Biochemistry and Molecular Biology, Medical School of Henan University, Kaifeng, Henan, 475004 China.
authors.forename: Xiangqian
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305 USA.
authors.forename: Erna
authors.initials: E
authors.lastname: Forgó
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305 USA.
authors.forename: Matt
authors.initials: M
authors.lastname: van de Rijn
keywords: 3’ end RNA sequencing; Leiomyosarcoma; expression profiling; subtypes