Progress Report 2013

Alan Rosenthal Research Fund March 2013 | Memorial Sloan-Kettering Cancer Center

Introduction

Memorial Sloan-Kettering Cancer Center physicians and scientists wish to transform the treatment of hemangiopericytoma. To accomplish this, we seek to identify and understand the complex drivers of the disease. And armed with this knowledge, we wish to create highly active therapies that can be combined, based on the particular makeup of a patient's cancer.

Recurrent Mutations in Hemangiopericytoma

Comprehensive clinical sequencing represents a new wave in cancer research. This process looks in detail at the entire genetic profile of a tumor sample, with the goal of identifying the errors that drive and support the cancer's rowth. By pinpointing these genetic faults, researchers can work to match drugs and compounds that have the ability curb or neutralize them -- halting the disease.

In a recent landmark study conducted by Drs. Mary Louise Keohan, Cristina Antonescu and their collaborators, a 44-year-old woman with cellular solitary fibrous tumor/hemangiopericytoma (SFT/HPC) was enrolled in a clinical sequencing program. The patient underwent both whole exome (determines the complete DNA sequence of hereditary information) and transciptome sequencing (shows when and where each gene is turned on/off in cells and tissues).

This process revealed a critical gene fusion between two proteins. The transcriptional repressor NAB2 is a protein that prevents genetic transcription (when a particular segment of DNA is copied into RNA). The transcriptional activator STAT6 is a protein that increases genetic transcription. Sequencing of the 44-year-old patient revealed that NAB2 and STAT6 join together to become a fusion gene, which performs a different function from the two individual genes - and in this case, the function relates directly to cancer growth.

Transcriptome sequencing of 27 additional SFT/HPC tumor samples showed the same gene fusion in every sample. In an additional set of 51 SFT/HPC tumors, the gene fusion was once again identified in all samples. Moreover, over-expression of the gene fusion in cells cultured in the lab resulted in growth consistent with cancer. These breakthrough studies establish the NAB2-STAT6 fusion as the defining driver mutation of SFT/HPC.Drs. Keohan and Antonescu wish to launch a new era of personalized medicine in hemagiopericytoma. Their next step is to identify drugs and compounds that work against this fusion, so they can develop powerful new treatments. Ultimately, their vision is that patients' tumors will be treated based upon their underlying genetic makeup, providing the best hope for full, permanent cure.

Conclusion

Our mission is to bring hemangiopericytoma patients best outcomes and highest quality of life. We believe that philanthropy is invaluable in carrying out this work and we are deeply grateful for the Alan Rosenthal Fund's support, which has allowed us to test promising theories and breakthroughs as they emerge.