Genomic Index Biomarker Identifies Those at Risk of Synovial Sarcoma Metastasis

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(ChemotherapyAdvisor) – Development of metastasis in synovial sarcoma is strongly associated with chromosome complexity, which helps explain why adults more frequently have metastasis than children: the adult genome is more frequently rearranged, a biomarker study reported in the Journal of Clinical Oncology published online January 14, 2013.

Noting the genetic basis of synovial sarcoma remains poorly understood, Frédéric Chibon, PhD, of the Tumor Genetics-Department of Pathology, Institut Bergonié, Bordeaux, France, and colleagues investigated whether their recently established 67-gene prognostic signature, CINSARC: Complexity Index in Sarcoma—which has application in gastrointestinal stromal tumors—and a subsequently identified Genomic Index biomarker could predict outcomes in patients with synovial sarcoma.

The investigators selected 100 patients with primary untreated synovial sarcoma tumors for expression and training/validation.

They found both CINSARC and the Genomic Index to have strong independent and validated prognostic values (P<0.001).

“By comparing expression profiles of tumors with or without metastasis, 14 genes that are common to the CINSARC signature were identified, and the two top-ranked genes, KIF14 and CDCA2, were validated as prognostic markers in an independent cohort,” Dr. Chibon reported.

When genomic profiles of adult versus pediatric patients with synovial sarcoma were compared, the researchers found metastasis was associated with genome complexity in both situations, with the adult genome more frequently rearranged. “Accordingly, pediatric patients with an even genomic profile do not develop metastasis,” he added.

“Given that the initial genetic driver event (the t(X;18) translocation) is the same for both situations, this is likely to mean that an independent, still unknown mechanism is permissive to chromosome instability in adult patients and resistant in pediatric patients,” they concluded.

The investigators now plan to validate the Genomic Index in a prospective study as decision criteria for clinical management of patients with synovial sarcoma.


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