Funded Research

August 15, 2008: The Liddy Shriver Sarcoma Initiative is funding a 1-year, $50,000 research study, "High throughput miRNA expression profiling for well differentiated and de-differentiated liposarcoma." The funding of this grant is made possible by a generous gift from the Keating family in honor of James Keating and by a generous gift from Laura Somerville, MD, PhD.

The study is being conducted by Dina Lev, MD in the Department of Cancer Biology at the the University of Texas M. D. Anderson Cancer Center in Houston, Texas and her co-investigator, Matt van de Rijn, MD, PhD, Professor of Pathology at the Stanford University School of Medicine in Stanford, California. The following statements appear in the abstract of their grant application:

Based on clinical observations, it is critical to better understand the molecular determinants differentiating well differentiated liposarcoma (WD LPS), a locally growing non-metastatic relatively favorable prognosis lesion from dedifferentiated liposarcoma (DD LPS), a highly metastatic poor prognosis malignancy. Furthermore, because these two sarcoma subtypes could represent a disease continuum, it would be extremely important to identify molecular aberrations that might accurately predict which WDLPS has the potential for more aggressive dedifferentiation. There is increasing evidence that miRNA dysregulation plays a role in tumorigenesis, cancer progression and metastasis; however, there is no data regarding miRNA expression and dysregulation in LPS. The purpose of the current proposal is to therefore provide initial insights into miRNA expression profiles of WD LPS and DD LPS. Towards that end we propose to conduct global miRNA expression profiling, using high throughput miRNA arrays, in a cohort of human LPS. Studied frozen human samples will include WD LPS and matched autologous normal fat, as well as DD LPS where samples of the WD and DD portions of these tumors as well as matched normal fat will be evaluated. Comprehensive statistical/bioinformatic analysis will be conducted to identify miRNAs that are selectively dysregulated in either of these LPS subtypes and to establish the differences in miRNA expression profiles that distinguish between them. Furthermore, we will evaluate the possible differences between miRNA in pure WD tumors versus that in the WD portions of DD LPS, with the hope of identifying miRNA expression patterns predicting sarcomagenic progression. Identified miRNA patterns will be further validated by quantitative RT-PCR examination of a large cohort of paraffin-imbedded archival LPS specimens. The proposed study is intended as an initial step to evaluate the differential expression of miRNAs, a new class of RNAs recently identified as very important in tumorigenesis and cancer progression, in WDLPS and DDLPS. Results of this initial study will hopefully form the basis of future investigations examining miRNAs as prognostic and therapeutic markers for LPS. As such, we hope that the proposed studies will both enhance our understanding of LPS biology and also advance LPS research.

You can read more about the approach they are taking in this study in his article, High throughput miRNA expression profiling for well differentiated and de-differentiated liposarcoma, which appears in the August 2008 issue of ESUN.

Editor's Update: A progress report about this study was published in the February 2010 issue of ESUN.