Project description:Uterine leiomyosarcoma (ULMS) is a poorly understood gynecologic cancer with few effective treatments. This study explores molecular events involved in ULMS with the goal of identifying strategies. Genome-wide transcriptional profiling were used to compare clinically well-annotated specimens of myometrium, leiomyoma and leiomyosarcoma.
Project description:Leiomyosarcoma (LMS) is a malignant neoplasm of smooth muscle and is an aggressive soft tissue tumor, have complex genetic abnormalities and could be defined as three molecular subtypes. Since that the molecular heterogeneity of LMS, the pathogenesis analysis per subtype will be highly necessary and helpful to understand the etiology of this more common sarcoma. Within this study, we collected four Myometrium, three Leiomyoma, three LMS cell lines and 99 LMSs (GSE45510), performed the system-wide gene expression profiling by 3'end RNA Sequencing, and found that there are significant different molecular pathways along the pathogenesis for those three molecular subtypes.
Project description:Background: Undifferentiated pleomorphic sarcoma (UPS), used to be called malignant fibrous histiocytoma (MFH), is a malignant soft tissue tumor of uncertain origin, and is characterized by morphology. UPS often share similar morphological characters with other sarcomas, especially Leiomyosarcoma. Leiomyosarcoma (LMS) is another malignant soft tissue sarcoma with complex genomic abnormalities, origin from smooth muscle. As a result, development of gene signature and/or biomarkers distinguishing UPS and LMS will definitely help the pathologist to precisely diagnose those patients. However, in the past, UPS was reported to be indistinguishable with LMS by genomic profiles. Methods and Results: In this study, 3’ end RNA Sequencing (3SEQ) was used to expression profile 6 UPS and 99 LMS cases. Overall, UPS was undistinguished with LMS by 3SEQ data, however, when we stratified LMS into three subtypes, UPS was shown to share similar expression pattern with Subtype II LMS, but had distinct molecular expression patterns with Subtype I and Subtype III LMS. Additional Immunohistochemistry staining by using LMS Subtype I and Subtype II markers validated that UPSs were positive for Subtype II marker ARL4C, but negative for Subtype I marker LMOD1. Furthermore, CD4 was shown to be significantly more highly expressed in UPS than LMS in both mRNA and protein levels. Conclusion: This study first reported that UPS shared similar gene expression pattern with subtype II LMS and UPS recapitulated the expression profiles of subtype II LMS. In this study, 3’ end RNA Sequencing (3SEQ) was used to expression profile 6 UPS and 99 LMS cases. In order to explore the molecular differences between UPS and LMS, We analyzed the expression data by SAMseq to identify the genes which were significantly differently expressed between UPS and LMS, between UPS and each LMS subtype.
Project description:Unexpected malignant tumors are a rare finding after surgery for symptomatic leiomyomas but there is little doubt that morcellation of these lesions is associated with a higher risk of iatrogenic peritoneal spread compared to women having surgery without morcellation. Thus, the FDA has issued a warning against the use of power morcellation in the majority of women undergoing myomectomy or hysterectomy for treatment of fibroids. We present a case report of 50 year old patient with intervertebral disc degeneration and multiple uterine fibroids decided to have laparoscopic supracervical hysterectomy. 28 months later the patient cystic adnexal mass removed by laparotomy and histologically, classified as leiomyosarcoma (sample H_12814-15). 19 months after this latter surgery MRI revealed a 10 x 8 x 6 cm abdominal mass attached to the liver and numerous other nodules attached to the abdominal wall. We investigated genomic profiles of four samples obtained from initial surgery and the malignant tumor that appeared 16 month later by molecular inversion probe (MIP) array hybridization. DNA was extracted from FFPE Tissue Samples using Covaris adaptive focused acoutics (AFATM) and truXTRACTM FFPE DNA kit and subjected to CGH analysis using the Affymetrix OncoScan platform according to the manufacturers protocol.
Project description:Uterine leiomyosarcoma (ULMS) is a poorly understood gynecologic cancer with few effective treatments. This study explores molecular events involved in ULMS with the goal of identifying strategies. Overall design: Genome-wide transcriptional profiling were used to compare clinically well-annotated specimens of myometrium, leiomyoma and leiomyosarcoma.
Project description:To investigate the cytogenetic and large-scale chromosomal changes in involuted or non-involuted microGISTs using post-whole genome amplification (WGA) FFPE DNA materials Sixteen patients, total 19 FFPE tumor samples (block storage time 4 months to 9 years), including 16 microGISTs and 3 GISTs larger than 1 cm from the same patients harboring microGISTs. All FFPE tumor samples underwent DNA extraction and WGA (modified degenerate oligonucleotide PCR (DOP) method, provided by Sigma). For each tumor sample, a post-WGA DNA extract from the normal tissue in the same block (or block from the same patient with a block storage time differences less than 2 years) was obtained for tumor sample DNA co-hybridization. Tumor and normal areas of interest were marked and collected from 5- to 10-micron unstained or hematoxylin-stained sections by manual or laser (PixCell IITM, Arcturus Bioscience, CA, USA) microdissection. DNAs were then extracted. WGA was performed using GenomePlex® Tissue Whole Genome Amplification WGA5 kit (Sigma, Saint Louis, MO, USA; http://www.sigmaaldrich.com/) in parallel in accordance with the manufacturer's protocols. At least four independent experiments were concurrently performed per template amplification. Four separate WGA reaction products were pooled for each sample.