Extracted from the PNBFund last newsletter:
Major Events in Synovial Sarcoma Research
by Marc Ladanyi, MD
In this update, I would like to highlight three major events in our work on synovial sarcoma. First, our laboratory, as part of the MSKCC Sarcoma SPORE (Specialized Programs of Research Excellence) application, successfully competed for the NIH/NCI grant, which officially started in July of this year.
Within this four project grant, we have Project #4, “Elucidating SYT-SSX-dependent histone code alterations to guide targeted epigenetic therapy for synovial sarcoma”, a joint effort with the laboratory of Dr C. David Allis at Rockefeller University. The goal is to address the central role of SYTSSX-dependent epigenetic alterations in the biology of synovial sarcoma from mechanistic, global genomic, and preclinical perspectives. The SYT-SSX fusion oncoprotein functions as an aberrant transcriptional protein that causes abnormal gene expression by interacting with enzymes that, modify the proteins (histones) that hold DNA (genes) in an active or inactive conformation. This project brings together expertise in fundamental histone biology with experience in synovial sarcoma cell lineand human tissue-based translational research to develop a deeper understanding of SYT-SSXdependent histone alterations that could lead to more rational, more precisely targeted, and, hopefully, more effective epigenetic therapy for synovial sarcoma. Dr. Tatsuo Ito, a postdoctoral fellowin my laboratory who is supported in part by the Paul Nabil Bustany Fund, generated key preliminary data for this application and is now continuing this project.
Secondly, 2010 saw the publication of the report of the Sarcoma Genome Project, entitled “Subtypespecific genomic alterations define new targets for soft-tissue sarcoma therapy”, in the journal Nature Genetics. This is the result of a collaboration of the MSKCC Soft Tissue Sarcoma group with a group from the Broad Institute and Dana-Farber Cancer Institute, both in Boston. This consortium performed an integrative analysis of DNA sequence changes, DNA copy number changes and gene expression patterns in 207 sarcoma samples encompassing seven major subtypes, including 23 synovial sarcoma samples. This provided the largest amount of genomic data so far assembled on synovial sarcoma, highlighting frequent losses at chromosome region 3p and gains of chromosome region 12q.
Finally, a second postdoctoral fellow who focused on synovial sarcoma recently joined my laboratory, Dr. Yoshiyuki Suehara. Dr. Suehara brings a special expertise in proteomics and is currently working on follow-up studies on secernin. In a previous unpublished study, he found that secernin expression appears to be a significant predictor for metastasis and survival of patients with synovial sarcoma. He is now pursuing a number of projects to confirm and further understand this finding in our laboratory.
We are very grateful for the support provided by the Paul Nabil Bustany Fund for Synovial Sarcoma Research, which has provided seed money and support for our ongoing work on this deadly cancer.
Dr. Marc Ladanyi is the William Ruane Chair in Molecular Oncology at Memorial Sloan-Kettering Cancer
Center in New York.