Unknown,Transcriptomics,Genomics,Proteomics

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Examination of tumor samples obtained after laparoscopic supracervical hysterectomy and a derivative leiomyosarcoma

ABSTRACT: 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.

INSTRUMENT(S): GeneChipR Scanner 3000, Covaris M220, GeneChipR Hybridization Oven 645, GeneChip Fluidics Station 450

ORGANISM(S): Homo sapiens

SUBMITTER: Carsten Holzmann

PROVIDER: E-MTAB-6039 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Uterine leiomyomata, or fibroids, are benign tumors of the uterine myometrium that significantly affect up to 30% of reproductive-age women. Despite being the primary cause of hysterectomy in the United States, accounting for up to 200,000 procedures annually, the etiology of leiomyoma remains largely unknown. Due to the lack of an effective medicinal therapy for these tumors, this disease continues to have a tremendous negative impact on women’s health. As a basis for understanding leiomyoma pathogenesis and identifying targets for pharmacotherapy, we conducted transcriptional profiling of leiomyoma and unaffected myometrium from humans and Eker rats, the best characterized preclinical model of leiomyoma. A global comparison of mRNA from leiomyoma versus myometrium in human and rat identified a highly significant overlap of dysregulated gene expression in leiomyoma. An unbiased pathway analysis using a method of gene set enrichment based on the Sigpathway algorithm detected the mammalian target of rapamycin (mTOR) pathway as one of the most highly upregulated pathways in both human and rat tumors. Activation of this pathway was confirmed in both human and rat leiomyomata at the protein level via Western. Inhibition of mTOR in female Eker rats with the rapamycin analog WAY-129327 for 2 weeks decreased mTOR signaling and cell proliferation in tumors, and treatment for 4 months significantly decreased tumor incidence, multiplicity and size. These results identify dysregulated mTOR signaling as a component of leiomyoma etiology across species and directly demonstrate the dependence of these tumors on mTOR signaling for growth in the Eker rat. Modulation of this pathway warrants additional investigation as a potential therapy for uterine leiomyoma. Experiment Overall Design: We analyzed 1-3 leiomyoma or normal myometrium biopsies from each 23 woman undergoing hysterectomy for the treatment of uterine fibroids. tment and compared it leiomyoma and normal myometrium from the Eker rat model of uterine fibroids (N=14-15)

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Examination of tumor samples obtained after laparoscopic supracervical hysterectomy and a derivative leiomyosarcoma

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