International consensus for neuroblastoma molecular diagnostics: report from the International Neuroblastoma Risk Group (INRG) Biology Committee

TLDR

Neuroblastoma exemplifies how tumor genomics can guide prognosis and treatment, yet prior to 2004 there was no international consensus on markers, methods, or interpretation, limiting reliable risk assessment and translational research. The committee’s goal was to pinpoint highly prognostic genetic aberrations for the INRG risk classification and to establish precise definitions, decisive biomarkers, and standardized techniques. They reviewed the 8,800‑patient INRG database, compared standard operating procedures across cooperative groups, and reached consensus on methodology, nomenclature, and future directions. The analysis identified MYCN amplification, 11q23 allelic status, and ploidy as key biomarkers, leading to their inclusion in the INRG classification, adoption of standardized SOPs, and development of nomenclature criteria, thereby enabling uniform risk assignment and facilitating international research.

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.