Original articleFavorable outcome of triploid neuroblastomas: a contribution to the special oncogenesis of neuroblastoma
Introduction
In several publications during the last 20 years, ploidy of neuroblastoma cells was considered a central marker that predicted prognosis. Early cytogenetic studies showed a high frequency of structural alterations in tumors with a near-diploid or near-tetraploid karyotype, whereas near-triploid cases frequently lacked these changes [1]. Karyotype analyses of a larger series of favorable tumors diagnosed after neuroblastoma screening displayed many near-triploid cases [2]. Further ploidy analyses were performed using flow cytometry. Look et al. [3], [4] indicated an association between hyperdiploidy and long-term survival after treatment for children below 2 years of age. In contrast, a diploid content correlated with early treatment failure. Although other groups obtained similar results [5], [6], [7], [8], tumor ploidy has not been implemented as a therapy stratification parameter in all but one international study. The exception has been the U.S. Pediatric Oncology Group trials, where ploidy discriminates between intermediate- and low-risk treatment for patients with nonamplified stage 4S.
In this study, we performed karyotype analyses in combination with interphase fluorescence in situ hybridization (FISH) on a cohort of 36 neuroblastoma patients to ascertain the consistency between tumor ploidy and the polysomy status of chromosome 1 according to FISH. In addition, a second collective of 440 specimens was investigated using FISH to ascertain associations of polysomy 1 with the patient's age, stage, and structural chromosomal alteration, and to assess the prognostic influence of polysomy 1.
Section snippets
Materials and methods
A series of 36 neuroblastoma tumors were investigated using both karyotype analysis and interphase FISH. Tumor samples were processed as described in Betts et al. [9]. In a second cohort consisting of 440 neuroblastoma patients, the copy number of chromosome 1 as well as the status of 1p, 11q, and MYCN were determined according to interphase FISH. Tissue samples were collected in 85 hospitals in Germany and Switzerland which were participating in German cooperative trials NB90/NB95 and NB97.
Results
The results of conventional karyotyping and interphase FISH of our first cohort of 36 neuroblastoma samples are summarized in Table 1. The copy number of chromosome 1 assessed by FISH corresponded to the ploidy level in 31/36 patients (86%). Three near-diploid tumors and one near-tetraploid tumor displayed three copies of chromosome 1 according to FISH, and one near-triploid neuroblastoma showed a tetrasomy 1.
The polysomy status of chromosome 1, together with the status of 1p, 11q, and MYCN
Discussion
In a large series of 151 neuroblastomas, Kaneko et al. [13] described the relationship between the modal chromosome number and the number of chromosomes 1. Due to the close correlation between these parameters, the authors concluded that tumors with disomy or trisomy 1 might be considered as diploid or triploid. The present analyses of 36 tumors using FISH and chromosome karyotyping confirmed this observation with very similar findings. Therefore, we assessed the copy number of chromosome 1 by
Acknowledgments
This work was supported by the Deutsche Kinderkrebsstiftung e.V. and Tumour Bank Neuroblastoma of the competence network Paediatric Oncology and Haematology (KPOH).
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Conflict of interest statement: The authors disclose that they have no financial or personal relationships with other people or organizations that could inappropriately influence their work.