Favorable outcome of triploid neuroblastomas: a contribution to the special oncogenesis of neuroblastoma

Spitz, Ruediger; Betts, David R.; Simon, Thorsten; Boensch, Marc; Oestreich, Joern; Niggli, Felix; Ernestus, Karen; Berthold, Frank; Hero, Barbara

doi:10.1016/j.cancergencyto.2005.09.001

Cited by 33 publications

(29 citation statements)

References 18 publications

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“…However, the limited number of patients analysed and/or the short follow-up of those studies did not allow one to draw definitive conclusions on the prognostic impact of this detection. In addition, a large multicentre European study (Navarro et al, 2006) and several other national studies (Christiansen et al, 1995;Cheung et al, 1997;Ladenstein et al, 2001;Simon et al, 2003;Sano et al, 2006;Spitz et al, 2006) have indicated that stage and Myc-N status were the only independent risk factors for children with localised NB. However, Myc-N amplification is a relatively rare event, occurring, as in our series, in about 10% of localised NB patients (Haase et al, 1999;Perez et al, 2000;Henry et al, 2005;Maris, 2005) and is thus inadequate to identify all the patients who will eventually relapse.…”

Section: Discussionmentioning

confidence: 99%

“…Genetic abnormalities at chromosome 1p (Rubie et al, 1997a), 3p, 11q (Spitz et al, 2003;Attiyeh et al, 2005;Simon et al, 2006) and 17q (Brinkschmidt et al, 2001), as well as biochemical (Simon et al, 2003), histological (Perez et al, 2000;Navarro et al, 2006;Sano et al, 2006), and biological factors (Christiansen et al, 1995;Cheung et al, 1997;Kramer et al, 1997;Perez et al, 2000;Ladenstein et al, 2001;Mora et al, 2001;Krams et al, 2003;Riley et al, 2004;Haber et al, 2006;Spitz et al, 2006), do not seem to have the same relevance in patients with localised NB as they do in patients with metastatic disease. Gene expression profiling and GCH studies have suggested specific favourable and unfavourable NB signatures (Takita et al, 2004;Ohira et al, 2005;Vandesompele et al, 2005), but presently a widespread identification of patients at risk of relapse by these techniques cannot be envisaged.…”

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confidence: 99%

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Detection of GD2-positive cells in bone marrow samples and survival of patients with localised neuroblastoma

et al. 2008

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The impact of bone marrow (BM) GD2-positive cells on survival has been evaluated in 145 Italian children with localised neuroblastoma (NB) evaluated at diagnosis by anti-GD2 immunocytochemistry. Nineteen of these (13.1%) were found to be BM GD2-positive, with the number of positive cells ranging between 1 and 155 out of 1 Â 10 6 total cells analysed. Seven/19 (38.8%) GD2-positive vs 12/126 (9.5%) GD2-negative patients relapsed. The 5-year event-free survival (EFS) and overall survival of the GD2-positive patients was significantly worse than that of the GD2-negative ones (62.2 vs 89.9%, Po0.001; and 74.9 vs 95.9%, P ¼ 0.005, respectively). GD2 positivity was not associated to other known risk factors, and in particular to Myc-N amplification and 1p deletion. Among Myc-N-negative patients, the EFS of those negative for both GD2 and 1p deletion was significantly better than in children positive for either one of these two markers (EFS ¼ 96.9 vs 66.0%, Po0.001). In conclusion, GD2 positivity may represent a prognostic marker for patients with non-metastatic NB without Myc-N amplification, and its combination with genetic alterations might help identifying patients that require a more careful follow-up.

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Section: Discussionmentioning

confidence: 99%

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Detection of GD2-positive cells in bone marrow samples and survival of patients with localised neuroblastoma

et al. 2008

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“…It is further implied that enforcement of polyploidy should be considered as means to attenuate tumor progression. Indeed, increased chromosomal content occasionally serves to decrease tumorigenic potential, as in Down syndrome (39,40), or in neuroblastoma (41). Artificial tetraploidization also resulted in the suppression of H19 expression.…”

Section: Discussionmentioning

confidence: 99%

Polyploidization of Murine Mesenchymal Cells Is Associated with Suppression of the Long Noncoding RNA H19 and Reduced Tumorigenicity

et al. 2012

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Mesenchymal stromal cells (MSC) are used extensively in clinical trials; however, the possibility that MSCs have a potential for malignant transformation was raised. We examined the genomic stability versus the tumorforming capacity of multiple mouse MSCs. Murine MSCs have been shown to be less stable and more prone to malignant transformation than their human counterparts. A large series of independently isolated MSC populations exhibited low tumorigenic potential under syngeneic conditions, which increased in immunocompromised animals. Unexpectedly, higher ploidy correlated with reduced tumor-forming capacity. Furthermore, in both cultured MSCs and primary hepatocytes, polyploidization was associated with a dramatic decrease in the expression of the long noncoding RNA H19. Direct knockdown of H19 expression in diploid cells resulted in acquisition of polyploid cell traits. Moreover, artificial tetraploidization of diploid cancer cells led to a reduction of H19 levels, as well as to an attenuation of the tumorigenic potential. Polyploidy might therefore serve as a protective mechanism aimed at reducing malignant transformation through the involvement of the H19 regulatory long noncoding RNA. Cancer Res; 72(24); 6403-13. Ó2012 AACR.

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“…Clinical manifestations vary from aggressive malignant growth to spontaneous regression. Tumors with near-triploid karyotypes with numerical aberrations (i.e., whole-chromosome gains and losses) have a good prognosis, whereas tumors with neardiploid or near-tetraploid karyotypes and segmental rearrangements, including deletions of parts of chromosome arms 1p or 11q, gain of 17q, and amplification of the MYCN proto-oncogene, have a poor prognosis (1)(2)(3). Children under age 1 year with NB generally present with a localized tumor and have an excellent outcome, whereas older children more often have aggressive NB with a poor prognosis despite intensive treatment (4).…”

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High-risk neuroblastoma tumors with 11q-deletion display a poor prognostic, chromosome instability phenotype with later onset

Carén

Kryh²,

Nethander³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

208

240

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Analysis of chromosomal aberrations is used to determine the prognosis of neuroblastomas (NBs) and to aid treatment decisions. MYCN amplification (MNA) alone is an incomplete poor prognostic factor, and chromosome 11q status has recently been included in risk classification. We analyzed 165 NB tumors using high-density SNP microarrays and specifically compared the high-risk groups defined by MNA ( n = 37) and 11q-deletion ( n = 21). Median patient age at diagnosis was 21 months for MNA tumors and 42 months for 11q-deletion tumors, and median survival time after diagnosis was 16 months for MNA and 40 months for 11q deletion. Overall survival (at 8 years) was ∼35% in both groups. MNA and 11q deletion were almost mutually exclusive; only one case harbored both aberrations. The numbers of segmental aberrations differed significantly; the MNA group had a median of four aberrations, whereas the 11q-deletion group had 12. The high frequency of chromosomal breaks in the 11q-deletion group is suggestive of a chromosomal instability phenotype gene located in 11q; one such gene, H2AFX , is located in 11q23.3 (within the 11q-deletion region). Furthermore, in the groups with segmental aberrations without MNA or 11q deletion, the tumors with 17q gain have worse prognosis than those with segmental aberrations without 17q gain, which have a favorable outcome. This study has implications for therapy in different risk groups and stresses that genome-wide microarray analyses should be included in clinical management to fully evaluate risk, aid diagnosis, and guide treatment.

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Favorable outcome of triploid neuroblastomas: a contribution to the special oncogenesis of neuroblastoma

Cited by 33 publications

References 18 publications

Detection of GD2-positive cells in bone marrow samples and survival of patients with localised neuroblastoma

Detection of GD2-positive cells in bone marrow samples and survival of patients with localised neuroblastoma

Polyploidization of Murine Mesenchymal Cells Is Associated with Suppression of the Long Noncoding RNA H19 and Reduced Tumorigenicity

High-risk neuroblastoma tumors with 11q-deletion display a poor prognostic, chromosome instability phenotype with later onset

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