1. ¹CCRI, Children's Cancer Research Institute, Vienna, Austria
2. ²Center for Childhood Cancer Research, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, PA, USA
3. ³Children's Cancer Institute Australia, Sydney, Australia
4. ⁴National Cancer Institute, Bethesda, MD, USA
5. ⁵Chiba Cancer Center Research Institute, Japan
6. ⁶Institut Curie, Paris, France
7. ⁷Centre for Medical Genetics, Ghent, Belgium
8. ⁸University of Cologne, Germany
9. ⁹Children's Oncology Group Statistics and Data Center, University of Florida, Gainesville, FL, USA
10. ¹⁰The University of Chicago, Chicago, IL, USA
11. ¹¹Section of Paediatrics, Institute of Cancer Research and Royal Marsden Hospital, Surrey, UK

Correspondence: Dr PF Ambros and Dr IM Ambros, CCRI, Children's Cancer Research Institute, Kinderspitalgasse 6, Vienna A-1090, Austria. E-mail: ambros@ccri.at; Dr JM Maris, Division of Oncology, Children's Hospital of Philadelphia, ARC902A, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA. E-mail: maris@chop.edu

Received 30 September 2008; Revised 26 February 2009; Accepted 6 March 2009.

Abstract

Neuroblastoma serves as a paradigm for utilising tumour genomic data for determining patient prognosis and treatment allocation. However, before the establishment of the International Neuroblastoma Risk Group (INRG) Task Force in 2004, international consensus on markers, methodology, and data interpretation did not exist, compromising the reliability of decisive genetic markers and inhibiting translational research efforts. The objectives of the INRG Biology Committee were to identify highly prognostic genetic aberrations to be included in the new INRG risk classification schema and to develop precise definitions, decisive biomarkers, and technique standardisation. The review of the INRG database (n=8800 patients) by the INRG Task Force finally enabled the identification of the most significant neuroblastoma biomarkers. In addition, the Biology Committee compared the standard operating procedures of different cooperative groups to arrive at international consensus for methodology, nomenclature, and future directions. Consensus was reached to include MYCN status, 11q23 allelic status, and ploidy in the INRG classification system on the basis of an evidence-based review of the INRG database. Standardised operating procedures for analysing these genetic factors were adopted, and criteria for proper nomenclature were developed. Neuroblastoma treatment planning is highly dependant on tumour cell genomic features, and it is likely that a comprehensive panel of DNA-based biomarkers will be used in future risk assignment algorithms applying genome-wide techniques. Consensus on methodology and interpretation is essential for uniform INRG classification and will greatly facilitate international and cooperative clinical and translational research studies.