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Clin Cancer Res. 2015 Oct 15;21(20):4733-9. doi: 10.1158/1078-0432.CCR-14-3326.

Clinical Application of Prognostic Gene Expression Signature in Fusion Gene-Negative Rhabdomyosarcoma: A Report from the Children's Oncology Group.

Author information

1
Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, Arizona. phingorani@phoenixchildrens.com.
2
SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
3
Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom.
4
Department of Biostatistics, University of Nebraska Medical Center, Omaha, Nebraska.
5
Department of Pathology, Children's Hospital of Los Angeles, Los Angeles, California.
6
SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland. Ludwig Center for Cancer Research, Lausanne, Switzerland. Oncology Department, University of Lausanne, Lausanne, Switzerland.
7
The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
8
Division of Hematology/Oncology, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington.
9
Pauline Allen Gill Center for Cancer and Blood Disorders, Children's Medical Center, Dallas, Texas. Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.

Abstract

PURPOSE:

Pediatric rhabdomyosarcoma (RMS) has two common histologic subtypes: embryonal (ERMS) and alveolar (ARMS). PAX-FOXO1 fusion gene status is a more reliable prognostic marker than alveolar histology, whereas fusion gene-negative (FN) ARMS patients are clinically similar to ERMS patients. A five-gene expression signature (MG5) previously identified two diverse risk groups within the fusion gene-negative RMS (FN-RMS) patients, but this has not been independently validated. The goal of this study was to test whether expression of the MG5 metagene, measured using a technical platform that can be applied to routine pathology material, would correlate with outcome in a new cohort of patients with FN-RMS.

EXPERIMENTAL DESIGN:

Cases were taken from the Children's Oncology Group (COG) D9803 study of children with intermediate-risk RMS, and gene expression profiling for the MG5 genes was performed using the nCounter assay. The MG5 score was correlated with clinical and pathologic characteristics as well as overall and event-free survival.

RESULTS:

MG5 standardized score showed no significant association with any of the available clinicopathologic variables. The MG5 signature score showed a significant correlation with overall (N = 57; HR, 7.3; 95% CI, 1.9-27.0; P = 0.003) and failure-free survival (N = 57; HR, 6.1; 95% CI, 1.9-19.7; P = 0.002).

CONCLUSIONS:

This represents the first, validated molecular prognostic signature for children with FN-RMS who otherwise have intermediate-risk disease. The capacity to measure the expression of a small number of genes in routine pathology material and apply a simple mathematical formula to calculate the MG5 metagene score provides a clear path toward better risk stratification in future prospective clinical trials.

PMID:
26473193
PMCID:
PMC4610152
DOI:
10.1158/1078-0432.CCR-14-3326
[Indexed for MEDLINE]
Free PMC Article

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