Unequivocal Delineation of Clinicogenetic Subgroups and Development of a New Model for Improved Outcome Prediction in Neuroblastoma

Vandesompele, Jo; Baudis, Michael; Preter, Katleen De; Roy, Nadine Van; Ambros, Peter F.; Bown, Nick; Brinkschmidt, Christian; Christiansen, Holger; Combaret, Valérie; Łastowska, M; Nicholson, James C.; O’Meara, Anne; Plantaz, Dominique; Stallings, Raymond; Brichard, Bénédicte; Broecke, Caroline Van den; Bie, Sylvia De; Paepe, Anne De; Laureys, Geneviève; Speleman, Frank

doi:10.1200/jco.2005.06.104

Cited by 162 publications

(176 citation statements)

References 39 publications

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“…However, the analysis of type 2b profiles shows that 1p and 11q deletions are not exclusive. On the other hand, previous studies have shown that localised tumours or those occurring in infants o1 year of age have numerical rather than structural abnormalities (Bilke et al, 2005;Vandesompele et al, 2005). In our series, a type 1 genomic profile is also associated with an age o1 year at diagnosis and with localised disease.…”

Section: Discussionsupporting

confidence: 44%

“…A more recent study based on the pooled CGH data of 231 samples from several institutions has confirmed this classification (Vandesompele et al, 2005). Variations in the copy number of whole chromosomes was more frequently observed in localised disease, of favourable histology, and in infants, with recognition of a survivor signature conferring 100% 5-year survival in stage 1, 2 or 4s tumours presenting with whole chromosome 17 gain, whereas structural aberration patterns were a significant predictor of poorer outcome.…”

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confidence: 75%

“…Chromosome CGH, and more recently array-CGH, are techniques of choice for assessing such imbalances in a single experiment (Kallioniemi et al, 1992). To date, several series of CGH analyses of non-selected NBs including MYCN amplified cases have been published, mostly consisting of data from several centres (Brinkschmidt et al, 1997;Vandesompele et al, 2005). These previous analyses have shown that, using CGH, tumours could be classified into genomic groups associated with distinct clinical characteristics.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, it has been shown that the presence of structural abnormalities due to unbalanced chromosome translocations is clearly associated with advanced stages of disease Bilke et al, 2005;Vandesompele et al, 2005). These unbalanced translocations most frequently involve chromosome 17q as the donor and chromosomes 1p, 3p or 11q, amongst others, as the recipient chromosome, leading to genomic imbalance.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 44%

mentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2007

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“…Loss of chromosome 1p material, occurring predominately through an unbalanced t(1;17) that also results in gain of 17q (Van Roy et al, 1994), is a common chromosomal imbalance found in NB and occurs preferentially in tumors with MYCN amplification (MNA) (Fong et al, 1989). All three of these nonrandom genetic abnormalities, loss of 1p, gain of 17q and MNA, are independently associated with a poor clinical outcome (Brodeur et al, 1984;Spitz et al, 2003;Attiyeh et al, 2005;Vandesompele et al, 2005).…”

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confidence: 99%

MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells

2007

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Neuroblastoma (NB) is one of the most common forms of cancer in children, accounting for 15% of pediatric cancer deaths. The clinical course of these tumors is highly variable and is dependent on such factors as age at presentation, stage, ploidy and genomic abnormalities. Hemizygous deletion of chromosome 1p occurs in approximately 30% of advanced stage tumors, is associated with a poor prognosis, and likely leads to the loss of one or more tumor suppressor genes. We show here that microRNA (miRNA)-34a (1p36.23) is generally expressed at lower levels in unfavorable primary NB tumors and cell lines relative to normal adrenal tissue and that reintroduction of this miRNA into three different NB cell lines causes a dramatic reduction in cell proliferation through the induction of a caspase-dependent apoptotic pathway. As a potential mechanistic explanation for this observation, we demonstrate that miR-34a directly targets the messenger ribonucleic acid (mRNA) encoding E2F3 and significantly reduces the levels of E2F3 protein, a potent transcriptional inducer of cell-cycle progression. Furthermore, miR-34a expression increases during retinoic acidinduced differentiation of the SK-N-BE cell line, whereas E2F3 protein levels decrease. Thus, adding to the increasing role of miRNAs in cancer, miR-34a may act as a suppressor of NB tumorgenesis.

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Expression of two parental imprinted miRNAs improves the risk stratification of neuroblastoma patients

et al. 2014

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Age at diagnosis, stage, and MYCN amplification are the cornerstones of the risk-stratification score of neuroblastoma that enables defining patients at low- and high risk. Refinement of this stratification is needed to optimize standard treatment and to plan future clinical trials. We investigated whether two parental imprinted miRNAs (miR-487b and miR-516a-5p) may lead to a risk score with a better discrimination. Expression levels of maternal miR-487b and paternal miR-516a-5p were determined using quantitative RT-PCR both for 231 neuroblastoma tumors (derivation set) and 101 independent neuroblastoma tumors (validation set). Survival outcomes were overall survival (OS) and disease-free survival (DFS). Multivariable Cox models were developed from derivation set and their performance evaluated using Akaike's information criterion (AIC) (goodness-of-fit) and time-dependent area under curves (discrimination). The selected model was validated using internal and external validation. The prognostic model including current prognostic factors plus miR-487b, miR-516a-5p, and interaction between two miRNAs was selected. Performance of this model was better in terms of both predictive ability (smallest AIC) and discrimination power (AUC close to 0.70). This model identifies three risk groups: high (3), intermediate (2), and low (1). Hazard ratios (HR) across risk groups were HR2/1 = 6.3 (2.7–14.6), HR3/1 = 14.8 (7.2–30.2) for OS and HR2/1 = 2.8 (1.5–5.4), HR3/1 = 7.2 (3.9–13.4) for DFS. The rank between these three risk groups was maintained and validated when performing internal and external validation. Expression of maternal miR-487b and paternal miR-516a-5p improves the risk stratification. This better discrimination at diagnosis is of clinical utility both for current and future treatments of neuroblastoma patients.

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Unequivocal Delineation of Clinicogenetic Subgroups and Development of a New Model for Improved Outcome Prediction in Neuroblastoma

Cited by 162 publications

References 39 publications

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

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

MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells

Expression of two parental imprinted miRNAs improves the risk stratification of neuroblastoma patients

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