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Distribution of segmental chromosomal alterations in neuroblastoma

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Abstract

Background

Neuroblastoma (NB) is a heterogeneous tumor with extremely diverse prognosis according to clinical and genetic factors such as specific combinations of chromosomal imbalances.

Methods

Molecular karyotyping data from a national neuroblastic tumor database of 155 NB samples were analyzed and related to clinical data.

Results

Segmental chromosomal alterations (SCA) were detected in 102 NB, whereas 45 only displayed numerical alterations. Incidence of SCA was higher in stage M (92%) and MYCN amplified (MNA) NB (96%). Presence of SCA was associated with older age, especially 1q gain and 3p deletion. 96% of the deaths were observed in the SCA group and 85% of the relapsed NB contained SCA. The alteration most commonly associated with a higher number of other segmental rearrangements was 11q deletion, followed by 4p deletion. Whole-chromosome 19 gain was associated with lower stages, absence of SCA and better outcome.

Conclusions

SCA are not randomly distributed and are concentrated on recurrent chromosomes. The most frequently affected chromosomes identify prognostic factors in specific risk groups. SCA are associated with older age and MNA. We have identified a small subset of patients with better outcome that share whole-chromosome 19 numeric gain, suggesting its use as a prognostic biomarker in NB.

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Acknowledgements

We thank Desiree Ramal and Mireia Modesto for the data management in the study and all the Spanish hospitals that contributed with the cases reviewed. Hospital U i P La Fe is a full member of the “European Reference Network for paediatric Oncology (ERN-PAEDCAN)”.

Funding

No sources of study funding have been used.

Author information

Authors and Affiliations

  1. Pediatric Oncology and Hematology Unit, Hospital U i P La Fe, Av. Fernando Abril Martorell, 106, Valencia, Spain

    A. Juan Ribelles & A. Cañete

  2. Clinical and Translational Oncology Research Group, Instituto de Investigación La Fe, Valencia, Spain

    P. Gargallo, V. Segura, Y. Yáñez, J. Font de Mora & V. Castel

  3. Universitat de València, Valencia, Spain

    C. Ferriol & B. Juan

  4. Biostatistics Department, Instituto de Investigación La Fe, Valencia, Spain

    A. J. Cañada

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  1. A. Juan Ribelles
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Contributions

All the following authors: AJR, PG, CF, VS, YY, BJ, AJC, JFdeM, AC and VC have contributed to the work sufficiently. Main author: AJR. Contribution and correction of the manuscript: PG, VS, YY, AC, VC. Data collection and English translation: CF, BJ. Molecular karyotyping: AJC. Biostatistical analysis: JFdeM.

Corresponding author

Correspondence to A. Juan Ribelles.

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Conflict of interest

The authors declare no competing financial interests and no other non-financial competing interests.

Ethical approval (Research involving human participants and/or animals)

The study was approved by the Ethics and Investigation Committee Hospital U i P La Fe (CEIm). The study was performed according to the Declaration of Helsinki.

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All study actions were performed under the appropriate ethics code, and consent was obtained from all patients within the clinical trial recruited for treatment.

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Juan Ribelles, A., Gargallo, P., Ferriol, C. et al. Distribution of segmental chromosomal alterations in neuroblastoma. Clin Transl Oncol 23, 1096–1104 (2021). https://doi.org/10.1007/s12094-020-02497-2

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  • DOI: https://doi.org/10.1007/s12094-020-02497-2

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