Transcriptomics

Dataset Information

299

Stratification of Leiomyosarcoma molecular subtypes by 3' end RNA-sequencing: Toward precision medicine


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 demonstrate the existence of 3 molecular subtypes in a cohort of 99 cases and an independent cohort of 82 LMS. Two new FFPE tissue-compatible diagnostic immunohistochemical markers are identified: LMOD1 for subtype I LMS and ARL4C for subtype II LMS. Subtype I and subtype II LMS are associated with good and poor prognosis, respectively. The LMS subtypes show significant differences in expression levels for genes for which novel targeted therapies are being developed. Gene expression profiling was performed by 3' End RNA Sequencing (3SEQ), a next generation sequencing approach that does not rely on frozen tissue but can be performed on archival FFPE tissue. Samples included 99 LMS, 6 Undifferentiated Pleomorphic Sarcomas (UPS), 3 leiomyomas, 4 normal myometrium samples, and 1 case of Lymphangioleiomyomatosis (LAM). This study only includes the 99 LMS Samples. After gene expression levels were quantified by 3SEQ analysis pipeline, Consensus Clustering with bootstrap method was used to determine that the dataset contained three robust subtypes, and Silhouette analysis was performed to validate the subtype assignments. Two class SAM analysis (Significance Analysis of Microarrays) was performed to identify genes expressed differentially between each subtype of LMS with FDR of 0.05. Immunohistochemical staining was used to validate the potential diagnostic and prognostic markers from 3SEQ data on a tissue microarray.

ORGANISM(S): Homo sapiens  

SUBMITTER: Jonathan A Fletcher   Robert B West  Matt van de Rijn  Inigo Espinosa  Xiangqian Guo  Santosh Gupta  Shirley X Zhu  Sushama Varma  Alayne L Brunner  Cheng-Han Lee  Vickie Y Jo 

PROVIDER: E-GEOD-45510 | ArrayExpress | 2015-05-19

SECONDARY ACCESSION(S): SRP019994GSE45510PRJNA194525

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Clinically Relevant Molecular Subtypes in Leiomyosarcoma.

Guo Xiangqian X   Jo Vickie Y VY   Mills Anne M AM   Zhu Shirley X SX   Lee Cheng-Han CH   Espinosa Inigo I   Nucci Marisa R MR   Varma Sushama S   Forgó Erna E   Hastie Trevor T   Anderson Sharon S   Ganjoo Kristen K   Beck Andrew H AH   West Robert B RB   Fletcher Christopher D CD   van de Rijn Matt M  

Clinical cancer research : an official journal of the American Association for Cancer Research 20150420 15


Leiomyosarcoma is a malignant neoplasm with smooth muscle differentiation. Little is known about its molecular heterogeneity and no targeted therapy currently exists for leiomyosarcoma. Recognition of different molecular subtypes is necessary to evaluate novel therapeutic options. In a previous study on 51 leiomyosarcomas, we identified three molecular subtypes in leiomyosarcoma. The current study was performed to determine whether the existence of these subtypes could be confirmed in independen  ...[more]

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