Comparative genomic hybridization (CGH) analysis of stage 4 neuroblastoma reveals high frequency of 11q deletion in tumors lackingMYCN amplification

Plantaz, Dominique; Vandesompele, Jo; Roy, Nadine Van; Łastowska, M; Bown, Nick; Combaret, Valérie; Favrot, M.; Delattre, Olivier; Michon, Jean; Bénard, Jean; Hartmann, Olivier; Nicholson, James C.; Ross, Fiona; Brinkschmidt, Christian; Laureys, Geneviève; Caron, Huib N.; Matthay, Katherine K.; Feuerstein, Burt G.; Speleman, Frank

doi:10.1002/1097-0215(200002)9999:9999<::aid-ijc1114>3.0.co;2-r

Cited by 108 publications

(84 citation statements)

References 21 publications

(23 reference statements)

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“…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. The most frequent genomic imbalance observed in high risk NB is chromosome 17q gain (Lastowska et al, 1997;Bown et al, 1999), with other copy number changes involving chromosome 11q loss, often associated with chromosome 3p loss, in the absence of 1p loss (Breen et al, 2000;Plantaz et al, 2001). In this study, a clear association between the presence of genomic imbalances, as in type 2a and type 2b tumours, and advanced stage of disease is also observed.…”

Section: Discussionsupporting

confidence: 62%

“…Chromosome CGH analysis of NB samples has enabled the identification of distinct genetic subtypes with specific prognostic characteristics (Brinkschmidt et al, 1997(Brinkschmidt et al, , 1998Vandesompele et al, 1998Vandesompele et al, , 2001Plantaz et al, 2001). A genomic profile characterised by whole chromosome gains or losses, defining type 1 tumours , is observed more frequently in localised tumours and in children less than 1 year of age, with a good prognosis.…”

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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: 62%

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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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“…These data are consistent with previous reports on 3p25.3 status in neuroblastoma. 10 We profiled miR-885-5p expression by RT-qPCR in 60 primary neuroblastomas. For comparison, we profiled miR-331-3p, a miRNA possibly repressed by MYCN with tumor suppressive functions according to our previous data.…”

Section: Resultsmentioning

confidence: 99%

“…8,9 Neuroblastomas with poor outcome are subdivided into at least two biologically distinct groups, either with or without amplification of the MYCN oncogene. The second group frequently harbors segmental 3p deletions, 10 implying that neuroblastoma-suppressive transcripts are encoded from this region. Several efforts have been made to map and refine the critical region of 3p loss in neuroblastoma, currently assigned to 3p25-26.2, including the VHL gene.…”

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confidence: 99%

MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival

et al. 2011

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Several microRNA (miRNA) loci are found within genomic regions frequently deleted in primary neuroblastoma, including miR-885-5p at 3p25.3. In this study, we demonstrate that miR-885-5p is downregulated on loss of 3p25.3 region in neuroblastoma. Experimentally enforced miR-885-5p expression in neuroblastoma cell lines inhibits proliferation triggering cell cycle arrest, senescence and/or apoptosis. miR-885-5p leads to the accumulation of p53 protein and activates the p53 pathway, resulting in upregulation of p53 targets. Enforced miR-885-5p expression consistently leads to downregulation of cyclin-dependent kinase (CDK2) and mini-chromosome maintenance protein (MCM5). Both genes are targeted by miR-885-5p via predicted binding sites within the 3 0 -untranslated regions (UTRs) of CDK2 and MCM5. Transcript profiling after miR-885-5p introduction in neuroblastoma cells reveals alterations in expression of multiple genes, including several p53 target genes and a number of factors involved in p53 pathway activity. Taken together, these data provide evidence that miR-885-5p has a tumor suppressive role in neuroblastoma interfering with cell cycle progression and cell survival. Cell Death and Differentiation (2011) 18, 974-984; doi:10.1038/cdd.2010.164; published online 14 January 2011MicroRNAs (miRNAs) are non-coding short (18-24 nt) RNAs, controlling gene expression post trancriptionally, via inhibiting translation or triggering degradation of multiple target mRNAs. They are vitally important regulators of proliferation, differentiation and apoptosis. Upregulated and downregulated miRNAs have been found in different malignancies, implicating miRNAs as oncogenes or tumor suppressors. 1 The increasing body of evidence for miRNA involvement in tumorigenesis has prompted the search in cancer-associated genomic regions for miRNA loci. 2 In a deletion region at 13q14, miR-15 and miR-16, are downregulated in B-cell chronic lymphocytic leukemia. Both miR-15 and miR-16 negatively regulate BCL2 and positively regulate apoptosis, which could explain their frequent inactivation in leukemia. 3 Later, miR-34a at 1p36 emerged as a tumor suppressor gene (TSG). Several independent studies demonstrated anti-proliferative and pro-apoptotic potential of miR-34a. 4,5 The potential for involvement of as yet unreported miRNAs in cancer pathogenesis is great.Neural crest-derived neuroblastoma, one of the most common solid tumors in children, is frequently characterized as an 'enigmatic neoplasm'. Neuroblastoma has the highest rate of spontaneous regression of all human malignancies, however, B40% of neuroblastomas rapidly progress despite multimodal treatment regimes. 6,7 TP53 mutations are rare in neuroblastoma, which very often retain functional p53, suggesting that inhibitors of the p53 pathway or loss of p53 pathway positive regulators may be involved in neutralizing p53 activity. 8,9 Neuroblastomas with poor outcome are subdivided into at least two biologically distinct groups, either with or without amplification of the MYCN oncogene....

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“…In addition, hemizygous deletions in human neuroblastoma may lend further prognostic information (Maris and Matthay 1999;Maris et al 2000;Brodeur 2003;Maris and Shusterman 2003;Spitz et al 2003). Such deletions have been well characterized at 1p36 (Caron et al 1996a;Maris et al 2000), 11q14-23 (Guo et al 1999Luttikhuis et al 2001;Plantaz et al 2001;Spitz et al 2003), 3p14-25 (Ejeskar et al 1998;Breen et al 2000;Spitz et al 2003), 4p15-p16 (Caron et al 1996b;Perri et al 2002), 5q (Meltzer et al 1996), 9p21 (Marshall et al 1997), 14q32 , 16p12-p13 , 18q21 (Reale et al 1996), and 19q13 (Mora et al 2001).…”

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confidence: 99%

Region-specific detection of neuroblastoma loss of heterozygosity at multiple loci simultaneously using a SNP-based tag-array platform

Maris

Hii²,

Gelfand³

et al. 2005

Genome Res.

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Many cancers are characterized by chromosomal aberrations that may be predictive of disease outcome. Human neuroblastomas are characterized by somatically acquired copy number changes, including loss of heterozygosity (LOH) at multiple chromosomal loci, and these aberrations are strongly associated with clinical phenotype including patient outcome. We developed a method to assess region-specific LOH by genotyping multiple SNPs simultaneously in DNA from tumor tissues. We identified informative SNPs at an average 293-kb density across nine regions of recurrent LOH in human neuroblastomas. We also identified SNPs in two copy number neutral regions, as well as two regions of copy number gain. SNPs were PCR-amplified in 12-plex reactions and used in solution-phase single-nucleotide extension incorporating tagged dideoxynucleotides. Each extension primer had 5′ complementarity to one of 2000 oligonucleotides on a commercially available tag-array platform allowing for solid-phase sorting and identification of individual SNPs. This approach allowed for simultaneous detection of multiple regions of LOH in six human neuroblastoma-derived cell lines, and, more importantly, 14 human neuroblastoma primary tumors. Concordance with conventional genotyping was nearly absolute. Detection of LOH in this assay may not require comparison to matched normal DNAs because of the redundancy of informative SNPs in each region. The customized tag-array system for LOH detection described here is rapid, results in parallel assessment of multiple genomic alterations, and may speed identification of and/or assaying prognostically relevant DNA copy number alterations in many human cancers

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Comparative genomic hybridization (CGH) analysis of stage 4 neuroblastoma reveals high frequency of 11q deletion in tumors lackingMYCN amplification

Cited by 108 publications

References 21 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 miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival

Region-specific detection of neuroblastoma loss of heterozygosity at multiple loci simultaneously using a SNP-based tag-array platform

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