Prognostic Tool Reveals Childhood Cancer Subtype

An advanced technology called molecular inversion probes (MIPs) has been used to analyze DNA changes in the genome of Ewing sarcoma (ES) tumors.

The method has revealed a previously unknown sarcoma subtype, genetic factors related to long-term survival, and identification of a genetic change between the primary and metastatic stages of the disease that could lead to better, more targeted treatment.

A team of scientists at the Huntsman Cancer Institute (HCI) at the University of Utah (Salt Lake City, UT, USA) studied clinically archived formalin-fixed paraffin-embedded (FFPE) scrolls from 51 individual patients diagnosed with ES between November 1997 and June 2010. Twenty patients were confirmed by split Ewing sarcoma breakpoint region 1 (EWSR1) fluorescence in situ hybridization (FISH) probe, polymerase chain reaction (PCR), or t(11; 22) karyogram. The investigators looked at the relationship between the Ewing sarcoma genome and patient outcomes and found factors in eight areas of the genome correlated in varying degrees with long-term survival after diagnosis.

MIPs gave very high quality, genome-wide, high-resolution DNA analysis for clinical samples that have been preserved in formalin and encased in paraffin wax blocks, the process known as FFPE. Up to 10% of the tumor samples revealed that DNA in a specific region of the genome was missing, including a gene called the SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1 (SMARCB1). The same deletion had been described before in another aggressive and deadly sarcoma called a rhabdoid tumor. Pathologists double-checked the diagnosis on these samples and determined that they were not misdiagnosed rhabdoid tumors, but were indeed Ewing sarcoma that also had this rhabdoid characteristic.

Joshua Schiffman, MD, associate professor of pediatrics at the University of Utah and an HCI investigator, said "We found a specific gene that was present only in the metastatic tumors and not the primary tumor or normal cells. That gene has been described before in relation to other types of cancers, but not Ewing sarcoma. People do not die from a primary tumor. It is cancer metastasizing and spreading through the body that kills. As we learn what makes tumors metastatic, we can search for treatments that may keep primary tumors from making that change or target this specific change once it already has occurred in metastatic tumors." The study was published on August 4, 2012, in the journal Cancer Genetics.

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Huntsman Cancer Institute