Role of Ploidy, Chromosome 1p, and Schwann Cells in the Maturation of Neuroblastoma

Ambros, Ingeborg M.; Zellner, Andrea; Roald, Borghild; Amann, Gabriele; Ladenstein, Ruth; Printz, Dieter; Gadner, Helmut; Ambros, Peter F.

doi:10.1056/nejm199606063342304

Cited by 234 publications

(166 citation statements)

References 47 publications

Supporting

Mentioning

155

Contrasting

Unclassified

Order By: Relevance

“…Although 1 study has suggested that the Schwann cell component of ganglioneuromas originates from the tumor itself, 33 this study was disputed by others who found evidence that the Schwann cells represent an infiltrate of normal cells in the tumor. [53][54][55] The observation that DKK3 is highly expressed in the most differentiated tumor cells as well as in the presumably normal Schwann cells, suggests a more general association of high DKK3 expression and differentiation in cells from the neuroectodermal lineage.…”

Section: Discussionmentioning

confidence: 99%

“…Ganglioneuromas, in contrast, have a strong Schwann cell component. 2 The Schwann cells are presumably of nontumor origin, 4 although this has been topic of debate. 33 This raises the question whether the high DKK3 expression in ganglioneuromas might be derived from the Schwann cell component.…”

Section: High Dkk3 Expression In Ganglioneuroma and Ganglioneuroblastmentioning

confidence: 99%

“…3 This is supported by the observations that malignant neuroblastomas sometimes mature into the less aggressive ganglioneuroblastomas and even to the benign ganglioneuromas. 1 Although Schwannian stroma cells have been implicated in differentiation of neuroblastomas into ganglioneuromas, 4 little is known of the molecular background of neuroblastic tumor maturation. Gene expression profiles generated of neuroblastic tumors recently identified a limited number of genes which are differentially expressed between the 3 subtypes of tumors, including the epithelial membrane protein 3.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dickkopf‐3 expression is a marker for neuroblastic tumor maturation and is down‐regulated by MYCN

Koppen

Ait-Aissa

Koster

et al. 2008

Intl Journal of Cancer

View full text Add to dashboard Cite

Neuroblastoma and ganglioneuroma are neuroblastic tumors originating from the developing sympathetic peripheral nervous system. Ganglioneuromas are usually benign, while neuroblastomas have a variable prognosis and include very aggressive tumors. Examples exist of neuroblastomas regressing to ganglioneuromas and ganglioneuromas progressing to neuroblastomas. Little is known of the molecular differences between the tumor types. Here we report that Dickkopf-3 (DKK3), a putative extra cellular inhibitor of the Wnt/b-catenin pathway, showed a strongly differential expression between neuroblastoma and ganglioneuroma. Microarray analyses of 109 neuroblastic tumors revealed that DKK3 is strongly expressed in ganglioneuroma but only weakly in neuroblastoma. Low DKK3 expression in neuroblastoma correlated with a poor prognosis. The expression of DKK3 in the tumor series and in neuroblastoma cell lines was inversely correlated with the expression of the MYCN oncogene. Analysis of 2 neuroblastoma cell lines with inducible activity of MYCN showed that DKK3 is down-regulated by MYCN. We subsequently generated cell lines with inducible expression of DKK3, which revealed an inhibitory effect of DKK3 on proliferation. High DKK3 expression in the benign ganglioneuromas and down-regulation of DKK3 by MYCN in neuroblastoma might contribute to the strongly different clinical behavior of both neuroblastic tumor types. ' 2007 Wiley-Liss, Inc.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: High Dkk3 Expression In Ganglioneuroma and Ganglioneuroblastmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dickkopf‐3 expression is a marker for neuroblastic tumor maturation and is down‐regulated by MYCN

Koppen

Ait-Aissa

Koster

et al. 2008

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…In the case of adult cancers, DTCs are generally considered to be metastasis precursor cells 1 CCRI, Children's Cancer Research Institute, Vienna, Austria. 2 St. Anna Children's Hospital, Vienna, Austria. 3 Department of Pediatrics, Medical University of Innsbruck, Innsbruck, Austria.…”

Section: Introductionmentioning

confidence: 99%

Impact of Disseminated Neuroblastoma Cells on the Identification of the Relapse-Seeding Clone

Abbasi

Rifatbegovic

Brunner

et al. 2017

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

Purpose: Tumor relapse is the most frequent cause of death in stage 4 neuroblastomas. Since genomic information on the relapse precursor cells could guide targeted therapy, our aim was to find the most appropriate tissue for identifying relapse-seeding clones.Experimental design: We analyzed 10 geographically and temporally separated samples of a single patient by SNP array and validated the data in 154 stage 4 patients.Results: In the case study, aberrations unique to certain tissues and time points were evident besides concordant aberrations shared by all samples. Diagnostic bone marrowderived disseminated tumor cells (DTCs) as well as the metastatic tumor and DTCs at relapse displayed a 1q deletion, not detected in any of the seven primary tumor samples. In the validation cohort, the frequency of 1q deletion was 17.8%, 10%, and 27.5% in the diagnostic DTCs, diagnostic tumors, and DTCs at relapse, respectively. This aberration was significantly associated with 19q and ATRX deletions. We observed a significant increased likelihood of an adverse event in the presence of 19q deletion in the diagnostic DTCs.Conclusions: Different frequencies of 1q and 19q deletions in the primary tumors as compared with DTCs, their relatively high frequency at relapse, and their effect on event-free survival (19q deletion) indicate the relevance of analyzing diagnostic DTCs. Our data support the hypothesis of a branched clonal evolution and a parallel progression of primary and metastatic tumor cells. Therefore, searching for biomarkers to identify the relapse-seeding clone should involve diagnostic DTCs alongside the tumor tissue. Clin Cancer Res; 23(15); 4224-32.Ó2017 AACR.

show abstract

“…Aneuploidy is a commonly observed feature in neuroblastic tumours, and has been proposed to drive tumor development by enhancing genomic instability (Ambros et al, 1996). We reported the aneuploidies of chromosomes 3, 17, 18, 22 and X as common findings in 26 cells of patients.…”

Section: Discussionmentioning

confidence: 70%

Chromosome Imbalances and Alterations of AURKA and MYCN Genes in Children with Neuroblastoma

Yılmaz¹,

Demırhan²,

Erdoğan³

et al. 2012

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Background: Neuroblastoma (NB), like most human cancers, is characterized by genomic instability, manifested at the chromosomal level as allelic gain, loss or rearrangement. Genetics methods, as well as conventional and molecular cytogenetics may provide valuable clues for the identification of target loci and successful search for major genes in neuroblastoma. We aimed to investigate AURKA and MYCN gene rearrangements and the chromosomal aberrations (CAs) to determine the prognosis of neuroblastoma. Methods: We performed cytogenetic analysis by G-banding in 25 cases [11 girls (44%) and 14 boys (66%)] and in 25 controls. Fluorescence in situ hybridization (FISH) with AURKA and MYCN gene probes was also used on interphase nuclei to screen for alterations. Results: Some 18.4% of patient cells exhibited CAs., with a significant difference between patient and control groups in the frequencies (P<0.0001). Some 72% of the cells had structural aberrations, and only 28% had numerical chnages in patients. Structural aberrations consisted of deletions, translocations, breaks and fragility in various chromosomes, 84% and 52% of the patients having deletions and translocations, respectively. Among these expressed CAs, there was a higher frequency at 1q21, 1q32, 2q21, 2q31, 2p24, 4q31, 9q11, 9q22, 13q14, 14q11.2, 14q24, and

show abstract

Role of Ploidy, Chromosome 1p, and Schwann Cells in the Maturation of Neuroblastoma

Cited by 234 publications

References 47 publications

Dickkopf‐3 expression is a marker for neuroblastic tumor maturation and is down‐regulated by MYCN

Dickkopf‐3 expression is a marker for neuroblastic tumor maturation and is down‐regulated by MYCN

Impact of Disseminated Neuroblastoma Cells on the Identification of the Relapse-Seeding Clone

Chromosome Imbalances and Alterations of AURKA and MYCN Genes in Children with Neuroblastoma

Contact Info

Product

Resources

About