Chromosome 6p22 Locus Associated with Clinically Aggressive Neuroblastoma

Maris, John M.; Mossé, Yaël P.; Bradfield, Jonathan P.; Hou, Cuiping; Monni, Stefano; Scott, Richard; Asgharzadeh, Shahab; Attiyeh, Edward F.; Diskin, Sharon J.; Laudenslager, Marci; Winter, Cynthia; Cole, Kristina A.; Glessner, Joseph T.; Kim, Cecilia; Frackelton, Edward C.; Casalunovo, Tracy; Eckert, Andrew W.; Capasso, Mario; Rappaport, Eric; McConville, Carmel; London, Wendy B.; Seeger, Robert C.; Rahman, Nazneen; Devoto, Marcella; Grant, Struan F A; Li, Hongzhe; Hákonarson, Hákon

doi:10.1056/nejmoa0708698

Cited by 270 publications

(264 citation statements)

References 29 publications

(32 reference statements)

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“…Genome-wide association studies (GWAS) have also identified additional germline genetic variants in neuroblastoma patients, including single-nucleotide polymorphisms in LIN28B, BARD1, and LMO1, among others [26][27][28][29] as well as other polymorphisms in other chromosomal regions yet to be fully characterized [30,31]. These polymorphisms occur relatively frequently in the general population and may contribute to the development of sporadic neuroblastoma, although the functional roles of these germline variants and other somatic alterations remain to be elucidated.…”

Section: Epidemiology and Geneticsmentioning

confidence: 99%

Overview and recent advances in the treatment of neuroblastoma

Whittle

Smith

Doherty

et al. 2017

Expert Review of Anticancer Therapy

298

237

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Introduction: Children with neuroblastoma have widely divergent outcomes, ranging from cure in >90% of patients with low risk disease to <50% for those with high risk disease. Recent research has shed light on the biology of neuroblastoma, allowing for more accurate risk stratification and treatment reduction in many cases, although newer treatment strategies for children with high-risk and relapsed neuroblastoma are needed to improve outcomes. Areas covered: Neuroblastoma epidemiology, diagnosis, risk stratification, and recent advances in treatment of both newly diagnosed and relapsed neuroblastoma. Expert commentary: The identification of newer tumor targets and of novel cell-mediated immunotherapy agents may lead to novel therapeutic approaches, and clinical trials for regimens designed to target individual genetic aberrations in tumors are underway. A combination of therapeutic modalities will likely be required to improve survival and cure rates for patients with high-risk neuroblastoma.ARTICLE HISTORY

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Section: Epidemiology and Geneticsmentioning

confidence: 99%

Overview and recent advances in the treatment of neuroblastoma

Whittle

Smith

Doherty

et al. 2017

Expert Review of Anticancer Therapy

298

237

View full text Add to dashboard Cite

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“…DNA from the tumor and blood or uninvolved bone marrow was prepared with the use of anion-exchange chromatography (QIAGEN). Samples were processed by the Center for Applied Genomics at Children's Hospital, which operates a high-throughput Illumina BeadLab Genotyping System that uses customized standard operating procedures based on the manufacturer's specifications (Peiffer et al 2006;Hakonarson et al 2007;Maris et al 2008). …”

Section: Snp Array Genotypingmentioning

confidence: 99%

Genomic copy number determination in cancer cells from single nucleotide polymorphism microarrays based on quantitative genotyping corrected for aneuploidy

Attiyeh¹,

Diskin²,

Attiyeh³

et al. 2009

Genome Res.

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Microarrays are frequently used to profile genome-wide copy number (CN) aberrations. While generally robust for detecting CN variants in germline DNA, the methods used to derive CN from signal intensity values have been suboptimal when applied to cancer genomes. The complexity of genomic aberrations in cancer makes it more difficult to discriminate between signal and noise, and measuring CN as a discrete variable does not account for tumor heterogeneity. Furthermore, standard normalization approaches detect CN changes relative to the overall DNA content, which is often not diploid in cancer. We propose an algorithm that uses the degree of allelic imbalance as well as probe intensity, with a correction for aneuploidy, for a quantitative CN assessment and scoring of allelic ratios. This algorithm results in a more precise definition of CN and allelic aberration in the cancer genome, which is essential for translational efforts focused on using these tools for molecular diagnostics and for the discovery of therapeutic targets.[The OverUnder algorithm is freely available at http://stokes.chop.edu/CancerCN.]

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“…In contrast, the genetic bases of sporadic neuroblastoma remain largely unknown 2, 3. Through a genomewide association study (GWAS) of sporadic neuroblastoma, we have reported common single nucleotide polymorphisms (SNPs) associated with neuroblastoma susceptibility at CASC15 4, BARD1 5, LMO1 6, DUSP12 7, HSD17B12 7, DDX4/IL31RA 7, HACE1 8 and LIN28B 8 loci. Importantly, many of these GWAS‐identified genes have been shown to be key factors in both initiating and sustaining tumorigenesis 6, 8, 9, 10, 11.…”

Section: Introductionmentioning

confidence: 99%

The functional variant rs34330 of CDKN1B is associated with risk of neuroblastoma

Capasso

McDaniel

Cimmino

et al. 2017

J Cellular Molecular Medi

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The genetic aetiology of sporadic neuroblastoma is still largely unknown. We have identified diverse neuroblastoma susceptibility loci by genomewide association studies (GWASs); however, additional SNPs that likely contribute to neuroblastoma susceptibility prompted this investigation for identification of additional variants that are likely hidden among signals discarded by the multiple testing corrections used in the analysis of genomewide data. There is evidence suggesting the CDKN1B, coding for the cycle inhibitor p27Kip1, is involved in neuroblastoma. We thus assess whether genetic variants of CDKN1B are associated with neuroblastoma. We imputed all possible genotypes across CDKN1B locus on a discovery case series of 2101 neuroblastoma patients and 4202 genetically matched controls of European ancestry. The most significantly associated rs34330 was analysed in an independent Italian cohort of 311 cases and 709 controls. In vitro functional analysis was carried out in HEK293T and in neuroblastoma cell line SHEP‐2, both transfected with pGL3‐CDKN1B‐CC or pGL3‐CDKN1B‐TT constructs. We identified an association of the rs34330 T allele (‐79C/T) with the neuroblastoma risk (Pcombined = 0.002; OR = 1.17). The risk allele (T) of this single nucleotide polymorphism led to a lower transcription rate in cells transfected with a luciferase reporter driven by the polymorphic p27Kip1 promoter (P < 0.05). Three independent sets of neuroblastoma tumours carrying ‐79TT genotype showed a tendency towards lower CDKN1B mRNA levels. Our study shows that a functional variant, associated with a reduced CDKN1B gene transcription, influences neuroblastoma susceptibility.

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Chromosome 6p22 Locus Associated with Clinically Aggressive Neuroblastoma

Abstract: Background-Neuroblastoma is a malignancy of the developing sympathetic nervous system that most commonly affects young children and is often lethal. The etiology of this embryonal cancer is not known.

Cited by 270 publications

References 29 publications

Overview and recent advances in the treatment of neuroblastoma

Overview and recent advances in the treatment of neuroblastoma

Genomic copy number determination in cancer cells from single nucleotide polymorphism microarrays based on quantitative genotyping corrected for aneuploidy

The functional variant rs34330 of CDKN1B is associated with risk of neuroblastoma

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