Differential gene expression in leiomyosarcoma

Abstract

BACKGROUND Leiomyosarcomas (LMS) are a common subtype of soft tissue sarcoma. The molecular causes of the disease remain unclear. METHODS In the current study, gene expression in LMS, leiomyomas, and normal myometrium was examined. RNA was prepared and gene expression was determined using microarray analysis arrays containing approximately 12,000 known genes and 48,000 expressed squence tags (ESTs). RESULTS A number of genes were found to be differentially expressed in these sample sets, and six genes including cyclin‐dependent kinase inhibitor 2A, diaphanous (Drosophila homolog) 3, doublecortin, calpain 6, interleukin‐17B, and proteolipid 1 were found to be overexpressed in LMS compared with normal myometrium and 18 other tissues. Sets of genes were identified whose expression could be used to cluster samples with either LMS, leiomyomas, or normal myometrium. CONCLUSIONS The authors concluded that differences in gene expression can be detected between LMS and leiomyomas, normal myometrium, and other tissues, and that these changes in gene expression may yield clues with regard to the pathophysiology of leiomyosarcoma. Cancer 2003;98:1029–38. © 2003 American Cancer Society. DOI 10.1002/cncr.11586

A Differentiation-Based MicroRNA Signature Identifies Leiomyosarcoma as a Mesenchymal Stem Cell-Related Malignancy

“…17 An adaptation of a previously published protocol 8 was used to achieve SMC differentiation. Briefly, hMSCs were seeded at 75-100 cells/mm 2 and, on near confluency, smooth muscle differentiation medium (SMDM) [MCDB131 (Sigma, St. Louis, MO) supplemented with 1% FBS and 100U/ml Heparin] was added. The thromboxane A 2 (TxA2)-induced method of differentiation was adapted from Kim et al 7 In brief, hMSCs were plated at 0.2 ϫ 10 6 cells per well in a 6-well plate, re-fed with fresh ␣ minimal essential media (␣MEM) with 0.25% FBS 24 hours before addition of 1.0 mol/L of the TxA2 chemical analog U46619 (Enzo Life Sciences, Farmingdale, NY).…”

“…1 Although generally accepted as tumors of SM origin, it has been hypothesized that ULM and uterine leiomyosarcomas (ULMS) are separate entities of independent cellular and/or molecular origin. 2 Smooth muscle is an involuntary nonstriated muscle that can be found throughout the body, within the vasculature and organs such as the uterus. The broad function of smooth muscle cells (SMCs) in these organs is to maintain organ structure and elicit necessary contractions, but specific actions, such as unique responses to environmental cues or rate of contractility, depend on the particular anatomical location.…”

Expression profile of tuberin and some potential tumorigenic factors in 60 patients with uterine leiomyomata

“…7 Gene chip studies have provided a means of identifying differentially expressed genes in leiomyomata. [8][9][10] A group of genes have been found either up-or downregulated in leiomyomata. None of them has been linked to the pathogenesis of the leiomyomata.…”

Aberrant expression and regulation of NR2F2 and CTNNB1 in uterine fibroids

“…Although a large number of genes are differentially expressed in fibroids compared with myometrium (Tsibris et al 2002, Skubitz & Skubitz 2003, Arslan et al 2005, Luo et al 2005a, 2005b, Zaitseva et al 2006, Dimitrova et al 2009, it is likely that most of these changes occur as a consequence of the fibroids' presence and do not cause fibroid development. We have targeted NR2F2 and CTNNB1 in this study based on their significant potential for a causal role in uterine fibroid pathophysiology , Tanwar et al 2009).…”

“…Currently, uterine fibroids are the single-most common reason for hysterectomy in developed countries (Treloar et al 1999, Farquhar & Steiner 2002, Garry 2005, and despite their large healthcare burden, there is limited understanding of the molecular mechanisms that drive fibroid pathophysiology. Gene profiling studies by our laboratory and others have identified a large number of genes with altered expression in fibroid tumours compared with myometrium (Tsibris et al 2002, Skubitz & Skubitz 2003, Arslan et al 2005, Luo et al 2005a, 2005b, Zaitseva et al 2006, Dimitrova et al 2009). However, it is hypothesised that the majority of these genes are differentially expressed as a consequence of the changed microenvironment caused by the fibroids' presence and are not causal to fibroid development.…”