Quality Assessment of Genetic Markers Used for Therapy Stratification

Ambros, Inge M.; Bénard, Jean; Boavida, Maria Guida; Bown, Nick; Caron, Huib N.; Combaret, Valérie; Couturier, Jérôme; Darnfors, Catarina; Delattre, Olivier; Freeman-Edward, J.; Gambini, Claudio; Groß, Nicole; Hattinger, Claudia Maria; Luegmayr, A.; Lunec, John; Martinsson, Tommy; Mazzocco, Katia; Navarro, Samuel; Noguera, Rosa; O’Neill, Seamus; Pötschger, Ulrike; Rumpler, S.; Speleman, Franki; Tonini, Gian Paolo; Valent, Alexander; Roy, Nadine Van; Amann, Gabriele; Bernardi, Bruno; Kogner, Per; Ladenstein, Ruth; Michon, Jean; Pearson, Adj; Ambros, Peter F.

doi:10.1200/jco.2003.03.025

Cited by 110 publications

(78 citation statements)

References 30 publications

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“…Because of the relative rarity of neuroblastomas, and the uniqueness of many of the molecular diagnostic factors, the INRG Biology Committee recommended that the genetic studies required for INRG classification be carried out in experienced laboratories, typically central reference laboratories for the cooperative groups (see Table 4), to guarantee high consistency and quality of results (Ambros et al, 2003).…”

Section: International Consensus By the Inrg Biology Committeementioning

confidence: 99%

“…However, the optimal combination of these and additional recently described prognostic biomarkers to build a treatment stratification algorithm has not been determined yet. Here, we present the consensus of the INRG Biology Committee on which markers should be used currently, on the standardised operating procedures (SOPs; partly on the basis of SIOPEN activities (Ambros et al, 2003)) for analysing neuroblastoma tumour molecular diagnostics and genetic nomenclature in this rapidly evolving field.…”

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confidence: 99%

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

Ambros¹,

Ambros²,

et al. 2009

Br J Cancer

351

285

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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 ¼ 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.

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Section: International Consensus By the Inrg Biology Committeementioning

confidence: 99%

mentioning

confidence: 99%

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

Ambros¹,

Ambros²,

et al. 2009

Br J Cancer

351

285

View full text Add to dashboard Cite

show abstract

“…To guarantee the reproducibility of the results, 11 laboratories from 9 European countries set up an European Neuroblastoma Quality Assessment (ENQUA) Group (Ambros et al, 2003). This led to the establishment of common rules with regard to the handling of tumour materials, methods, and DNA probes to be used, and the interpretation of DNA blots and fluorescent in situ hybridisation (FISH) analyses.…”

Section: Biological Studiesmentioning

confidence: 99%

Treatment of localised resectable neuroblastoma. Results of the LNESG1 study by the SIOP Europe Neuroblastoma Group

et al. 2008

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Main objective of this study was to confirm that surgery alone is an effective and safe treatment for localised resectable neuroblastoma except stage 2 with amplified MYCN gene (MYCNA). Of 427 eligible stages 1 -2 patients, 411 had normal MYCN and 16 had MYCNA. Of the 288 stage 1 patients with normal MYCN, 1 died of complications and 16 relapsed, 2 of whom died; 5-year relapse-free survival (RFS) and overall survival (OS) rates were 94.3% (95% confidence interval (CI): 91.6 -97) and 98.9% (95% CI: 97.7 -100), respectively. Of the 123 stage 2 patients with normal MYCN, 1 died of sepsis and 22 relapsed, 8 of whom died (RFS 82.8%, 95% CI: 76.2 -89.5; OS 93.2%, 95% CI: 88.7 -97.8). In stage 2, OS and RFS were worse for patients with elevated LDH and unfavourable histopathology. Of 16 children with MYCNA, 7 were stage 1 (5 relapses and 4 deaths) and 9 were stage 2 (3 relapses and 2 deaths) patients. In conclusion, surgery alone yielded excellent OS for both stage 1 and 2 neuroblastoma without MYCNA, although stage 2 patients with unfavourable histopathology and elevated LDH suffered a high number of relapses. Both stage 1 and 2 patients with MYCNA were at greater risk of relapse.

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“…Fine-needle aspirates were checked by the cytologist on May -Grünwald -Giemsa-stained spreads. Only cases with more than 60% tumour cells were included (Ambros et al, 2003). The MYCN status was assessed by FISH using a MYCN probe (Zymed Laboratories, San Francisco, CA, USA) on frozen sections for tumour fragments, and on cytogenetic preparations for fine-needle aspirates.…”

Section: Tumour Samplesmentioning

confidence: 99%

“…Until now, these various genetic markers are analysed separately by conventional karyotyping, 24-colour karyotyping, FISH and/or LOH studies (Ambros et al, 2003), making these analyses time consuming and rendering their interpretation difficult as not all markers could be studied at one time. During the last decade, pangenomic techniques such as comparative genomic hybridisation (CGH), which enable the analysis of the entire tumour genome in one step, identifying DNA copy number gains and losses across the whole karyotype, have been developed (Kallioniemi et al, 1992).…”

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confidence: 99%

Chromosomal CGH identifies patients with a higher risk of relapse in neuroblastoma without MYCN amplification

et al. 2007

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Whereas neuroblastoma (NB) with MYCN amplification presents a poor prognosis, no single marker allows to reliably predict outcome in tumours without MYCN amplification. We report here an extensive analysis of 147 NB samples at diagnosis, without MYCN amplification, by chromosomal comparative genomic hybridisation (CGH), providing a comprehensive overview of their genomic imbalances. Comparative genomic hybridisation profiles showed gains or losses of entire chromosomes (type 1) in 71 cases, whereas partial chromosome gains or losses (type 2), including gain involving 17q were observed in 68 cases. Atypical profiles were present in eight cases. A type 1 profile was observed more frequently in localised disease (Po0.0001), and in patients of less than 12 months at diagnosis (Po0.0001). A type 2 genomic profile was associated with a higher risk of relapse in the overall population (logrank test; Po0.0001), but also in the subgroup of patients with localised disease (log-rank test, P ¼ 0.007). In multivariate analysis, the genomic profile was the strongest independent prognostic factor. In conclusion, the genomic profile is of prognostic impact in patients without MYCN amplification, making it a help in the management of low-stage NB. Further studies using higher-resolution CGH are needed to better characterise atypical genomic alterations.

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Quality Assessment of Genetic Markers Used for Therapy Stratification

Cited by 110 publications

References 30 publications

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

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

Treatment of localised resectable neuroblastoma. Results of the LNESG1 study by the SIOP Europe Neuroblastoma Group

Chromosomal CGH identifies patients with a higher risk of relapse in neuroblastoma without MYCN amplification

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