Prognostic significance of DNA di-tetraploidy in neuroblastoma

Ladenstein, Ruth; Ambros, Inge M.; Pötschger, Ulrike; Amann, Gabriele; Urban, Christian; Fink, Franz Martin; Schimrigk, К.; Jones, Regina; Slociak, Margot; Schilling, F.; Ritter, J.; Berthold, Frank; Gadner, Helmut; Ambros, Peter F.

doi:10.1002/1096-911x(20010101)36:1<83::aid-mpo1020>3.0.co;2-9

Cited by 54 publications

(19 citation statements)

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“…However, the limited number of patients analysed and/or the short follow-up of those studies did not allow one to draw definitive conclusions on the prognostic impact of this detection. In addition, a large multicentre European study (Navarro et al, 2006) and several other national studies (Christiansen et al, 1995;Cheung et al, 1997;Ladenstein et al, 2001;Simon et al, 2003;Sano et al, 2006;Spitz et al, 2006) have indicated that stage and Myc-N status were the only independent risk factors for children with localised NB. However, Myc-N amplification is a relatively rare event, occurring, as in our series, in about 10% of localised NB patients (Haase et al, 1999;Perez et al, 2000;Henry et al, 2005;Maris, 2005) and is thus inadequate to identify all the patients who will eventually relapse.…”

Section: Discussionmentioning

confidence: 99%

“…Genetic abnormalities at chromosome 1p (Rubie et al, 1997a), 3p, 11q (Spitz et al, 2003;Attiyeh et al, 2005;Simon et al, 2006) and 17q (Brinkschmidt et al, 2001), as well as biochemical (Simon et al, 2003), histological (Perez et al, 2000;Navarro et al, 2006;Sano et al, 2006), and biological factors (Christiansen et al, 1995;Cheung et al, 1997;Kramer et al, 1997;Perez et al, 2000;Ladenstein et al, 2001;Mora et al, 2001;Krams et al, 2003;Riley et al, 2004;Haber et al, 2006;Spitz et al, 2006), do not seem to have the same relevance in patients with localised NB as they do in patients with metastatic disease. Gene expression profiling and GCH studies have suggested specific favourable and unfavourable NB signatures (Takita et al, 2004;Ohira et al, 2005;Vandesompele et al, 2005), but presently a widespread identification of patients at risk of relapse by these techniques cannot be envisaged.…”

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Detection of GD2-positive cells in bone marrow samples and survival of patients with localised neuroblastoma

et al. 2008

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The impact of bone marrow (BM) GD2-positive cells on survival has been evaluated in 145 Italian children with localised neuroblastoma (NB) evaluated at diagnosis by anti-GD2 immunocytochemistry. Nineteen of these (13.1%) were found to be BM GD2-positive, with the number of positive cells ranging between 1 and 155 out of 1 Â 10 6 total cells analysed. Seven/19 (38.8%) GD2-positive vs 12/126 (9.5%) GD2-negative patients relapsed. The 5-year event-free survival (EFS) and overall survival of the GD2-positive patients was significantly worse than that of the GD2-negative ones (62.2 vs 89.9%, Po0.001; and 74.9 vs 95.9%, P ¼ 0.005, respectively). GD2 positivity was not associated to other known risk factors, and in particular to Myc-N amplification and 1p deletion. Among Myc-N-negative patients, the EFS of those negative for both GD2 and 1p deletion was significantly better than in children positive for either one of these two markers (EFS ¼ 96.9 vs 66.0%, Po0.001). In conclusion, GD2 positivity may represent a prognostic marker for patients with non-metastatic NB without Myc-N amplification, and its combination with genetic alterations might help identifying patients that require a more careful follow-up.

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confidence: 99%

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Detection of GD2-positive cells in bone marrow samples and survival of patients with localised neuroblastoma

et al. 2008

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“…Although overall survival (OS) rates for high-risk neuroblastoma have improved only modestly over the past several decades, [1][2][3][4] there has been marked progress in the ability to recognize prognostic subgroups based on clinical and biological factors, 5 including age, [6][7][8] disease stage, 9 MYCN oncogene copy number (amplification), 10,11 DNA index (ploidy), 12,13 chromosomes 1 p36 and 11q23 deletions, 14 17 q gain 15 and histology. 16,17 Nowadays, patients with neuroblastoma are considered to be at high risk when presented with metastatic disease at an age above 12-18 months 7,8 as well as patients with MYCN-amplified tumours at any age.…”

Section: Introductionmentioning

confidence: 99%

28 years of high-dose therapy and SCT for neuroblastoma in Europe: lessons from more than 4000 procedures

Ladenstein

Pötschger

Hartman

et al. 2008

Bone Marrow Transplant

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Between 1978 and 2006, the European Group for Blood and Marrow Transplantation registered 4098 high-dose therapy (HDT) procedures followed by stem cell rescue (SCR) (3974 autologous/124 allogeneic) in patients with neuroblastoma. The 5-year rates for overall (OS) and event-free survival are 37 and 32%, respectively. The median age at diagnosis is 3.9 years (0.3-62 years) with 76 patients older than 18 years. Patients above 10 years carry a 2.5-fold higher risk. Younger patients cure significantly (o0.001) better with OS rates of 40 and 30% for age groups 2-4 years and 4-10 years, respectively. Their risks are about twofold higher than that of patients below 2 years with OS rates of 60%. The better the quality of remission status before HDT/SCT the better are the observed OS rates: 43% in CR1 (1199 patients) and 42% for CR2 (140 patients), and 36% for those in very good partial or partial remission (1413 patients) and 21% for those with sensitive relapse (134 patients). Patients reported with stable disease in first remission still had an OS rate of 30%. Multivariate analysis shows significantly better OS in the age group of less than 2 years (o0.0001), as well as a better quality of remission status before HDT/SCT (Po0.0001), with the use of peripheral stem cells (P ¼ 0.014), autologous SCT (P ¼ 0.031) and busulphan/melphalan HDT (Po0.001). Busulphan/melphalan HDT/SCT in first remission achieves an OS of 48%, while it is only 35% with other regimens (Po0.001), including melphalan alone, other melphalan-containing regimens, a variety of other drugs given as a single HDT as well as the addition of TBI or sequential HDT/SCT procedures. Further progress in the field may only be expected from large-scale international randomized trials.

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“…However, patient age and tumour stage alone cannot reliably predict tumour behaviour. Over the past two decades, tumour histology, (Shimada et al, 1999) status of the MYCN oncogene, (Brodeur et al, 1984;Seeger et al, 1985), and tumour cell DNA content (ploidy; Look et al, 1991;Ladenstein et al, 2001) have each been shown to be independently predictive of patient outcome in large retrospective and prospective studies. Besides these two genetic markers, recently 11q aberrations were also included in the INRG pretreatment risk classification (Cohn et al, 2009).…”

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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

352

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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Prognostic significance of DNA di-tetraploidy in neuroblastoma

Abstract: This analysis underlines the important influence of near di-tetraploidy on prognosis, and suggests that more efforts should be undertaken to implement this factor in future studies.

Cited by 54 publications

References 47 publications

Detection of GD2-positive cells in bone marrow samples and survival of patients with localised neuroblastoma

Detection of GD2-positive cells in bone marrow samples and survival of patients with localised neuroblastoma

28 years of high-dose therapy and SCT for neuroblastoma in Europe: lessons from more than 4000 procedures

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

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