Gain of Chromosome Arm 17q and Adverse Outcome in Patients with Neuroblastoma

Bown, Nick; Cotterill, SJ; Łastowska, M; O’Neill, Seamus; Pearson, Adj; Plantaz, Dominique; Meddeb, Mounira; Danglot, Gisèle; Brinkschmidt, Christian; Christiansen, Holger; Laureys, Geneviève; Speleman, Franki; Nicholson, James C.; Bernheim, Alain; Betts, David R.; Vandesompele, Jo; Roy, Nadine Van

doi:10.1056/nejm199906243402504

Cited by 463 publications

(363 citation statements)

References 25 publications

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“…In particular, gain of human chromosome 17q is frequently observed in human neuroblastomas, 22 and available evidence suggests that it is associated with aggressive, advanced stage disease and poor clinical outcome. 23 We have previously demonstrated that gain of chromosome 11, corresponding to 17q gain in humans, occurs in up to 30% of MYCN transgenic murine tumours and is one of the most common genetic changes observed in these tumours. [4][5][6] Furthermore, this region of gain is conserved in neuroblastomas occurring in man, mouse and rats.…”

Section: Discussionmentioning

confidence: 99%

Cell lines from MYCN transgenic murine tumours reflect the molecular and biological characteristics of human neuroblastoma

Cheng

Ford

et al. 2007

European Journal of Cancer

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Overexpression of the human MYCN oncogene driven by a tyrosine hydroxylase promoter causes tumours in transgenic mice that recapitulate the childhood cancer neuroblastoma. To establish an in vitro model to study this process, a series of isogenic cell lines were developed from these MYCN-driven murine tumours. Lines were established from tumours arising in homozygous and hemizygous MYCN transgenic mice. Hemizygous tumours gave rise to cell lines growing only in suspension. Homozygous tumours gave rise to similar suspension lines as well as morphologically distinct substrate-adherent lines characteristic of human S-type neuroblastoma cells. FISH analysis demonstrated selective MYCN transgene amplification in cell lines derived from hemizygous mice. Comparative genomic hybridisation (CGH) and fluorescence in situ hybridisation (FISH) analysis confirmed a range of neuroblastoma-associated genetic changes in the various lines, in particular, gain of regions syntenic with human 17q. These isogenic lines together with the transgenic mice thus represent valuable models for investigating the biological characteristics of aggressive neuroblastoma.

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Section: Discussionmentioning

confidence: 99%

Cell lines from MYCN transgenic murine tumours reflect the molecular and biological characteristics of human neuroblastoma

Cheng

Ford

et al. 2007

European Journal of Cancer

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“…59 This genetic abnormality is commonly due to an unbalanced translocation with a variety of partner chromosomes including chromosome 1. Gain of 17q is associated with advanced disease, age greater than 1 year, deletion of 1p, and amplification of MYCN.…”

Section: Discussionmentioning

confidence: 99%

Clinical Categories of Neuroblastoma Are Associated with Different Patterns of Loss of Heterozygosity on Chromosome Arm 1p

Mora

Cheung

Kushner

et al. 2000

The Journal of Molecular Diagnostics

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“…Amplification of the MYCN protooncogene was recognized as a strong independent adverse prognostic factor (in particular in patients with 1, 2, and 4S disease stage) (3) and has been widely used in treatment stratification. More recently, 17q gain was shown to be the most powerful predictive factor and for this reason 17q status is also being increasingly analyzed in clinical samples (4).…”

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confidence: 99%

Quantification of MYCN, DDX1, and NAG Gene Copy Number in Neuroblastoma Using a Real-Time Quantitative PCR Assay

et al. 2002

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Amplification of the proto-oncogene MYCN is a strong adverse prognostic factor in neuroblastoma patients in all tumor stages. The status of the MYCN gene has become an important factor in clinical decision making and therapy stratification. Consequently, fast and accurate assessment of MYCN gene copy number is of the utmost importance and the use of two independent methods to determine MYCN status is recommended. For these reasons we have developed and evaluated a real-time quantitative PCR (Q-PCR) assay as an alternative for timeconsuming Southern blot analysis (SB), and as a second independent technique in parallel with fluorescence in situ hybridization (FISH) analysis. Advantages of Q-PCR are a large dynamic range of quantification, no requirement for post-PCR sample handling and the need for very small amounts of starting material. The accuracy of the assay was illustrated by measurement of MYCN single gene copy changes in DNA samples of two patients with 2p deletion and duplication, respectively. Two different detection chemistries i.e., a sequence specific TaqMan probe and a generic DNA binding dye SYBR Green I were evaluated and shown to yield similar results. Also, two different calculation methods for copy number determination were used i.e., the kinetic method and the comparative C T method, and shown to be equivalent. In total, 175 neuroblastoma samples with known MYCN status, as determined by FISH and/or SB, were examined. Q-PCR data were highly concordant with FISH and SB data. In addition to MYCN copy number evaluation, DDX1 and NAG gene copy numbers were determined using a similar Q-PCR strategy. Survival analysis pointed out that DDX1 and/or NAG amplification has no additional adverse effect on prognosis.

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Gain of Chromosome Arm 17q and Adverse Outcome in Patients with Neuroblastoma

Abstract: Gain of chromosome segment 17q21-qter is an important prognostic factor in children with neuroblastoma.

Cited by 463 publications

References 25 publications

Cell lines from MYCN transgenic murine tumours reflect the molecular and biological characteristics of human neuroblastoma

Cell lines from MYCN transgenic murine tumours reflect the molecular and biological characteristics of human neuroblastoma

Clinical Categories of Neuroblastoma Are Associated with Different Patterns of Loss of Heterozygosity on Chromosome Arm 1p

Quantification of MYCN, DDX1, and NAG Gene Copy Number in Neuroblastoma Using a Real-Time Quantitative PCR Assay

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