Clinical Relevance of Tumor Cell Ploidy and N-myc Gene Amplification in Childhood Neuroblastoma: a Pediatric Oncology Group Study
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We assessed tumor cell DNA content (ploidy) and N-myc gene copy number as predictors of long-term disease-free survival in 298 children with neuroblastoma. Diploid tumor stem lines were identified in 101 patients (34%), clonal hyperdiploid abnormalities in 194 (65%), and hypodiploid stem lines in three (1%). In children with widely disseminated tumors at diagnosis (stage D), ploidy had a highly age-dependent influence on prognosis. Among infants (less than 12 months) treated with cyclophosphamide-doxorubicin, hyperdiploidy was closely associated with long-term disease-free survival (greater than 90% of cases), while diploidy invariably predicted early treatment failure (P less than .001). Similarly, in children 12 to 24 months of age who were treated with cisplatin-teniposide and cyclophosphamide-doxorubicin, diploidy uniformly predicted early failure, whereas half of the children with hyperdiploidy achieved long-term disease-free survival (P less than .001). There was no relationship between ploidy and treatment outcome in children older than 24 months with stage D tumors who had a very low probability of long-term disease-free survival (less than 10%). N-myc gene amplification was detected in 37 (25%) of the 147 tumors tested, with the remainder showing single-copy levels of the gene. N-myc gene amplification was more frequent in diploid than in hyperdiploid tumors (23 of 57 v 14 of 87, P = .001) and predicted a high likelihood of early treatment failure. In children younger than 2 years with disseminated neuroblastoma, tumor cell ploidy and N-myc gene copy number provide complementary prognostic information that will distinguish patients who can be cured on current regimens from those who require new treatment strategies.
Barr E, Naranjo A, Twist C, Tenney S, Schmidt M, London W Pediatr Blood Cancer. 2024; 71(8):e31089.
PMID: 38822537 PMC: 11318088. DOI: 10.1002/pbc.31089.
Hu X, Zhou Y, Hill C, Chen K, Cheng C, Liu X Br J Cancer. 2024; 130(11):1841-1854.
PMID: 38553589 PMC: 7616008. DOI: 10.1038/s41416-024-02666-y.
Computational completion of the Aurora interaction region of N-Myc in the Aurora a kinase complex.
Altiner P, Cinaroglu S, Timucin A, Timucin E Sci Rep. 2023; 13(1):18399.
PMID: 37884585 PMC: 10603048. DOI: 10.1038/s41598-023-45272-3.
Wieczorek A, Szewczyk K, Klekawka T, Stefanowicz J, Ussowicz M, Drabik G Front Oncol. 2023; 13:1134772.
PMID: 36865795 PMC: 9972431. DOI: 10.3389/fonc.2023.1134772.
as a potential oncogene and a prognostic biomarker for neuroblastoma.
Song J, Ni C, Dong X, Sheng C, Qu Y, Zhu L Front Oncol. 2022; 12:988415.
PMID: 36237324 PMC: 9552328. DOI: 10.3389/fonc.2022.988415.