Heterogeneous MYCN amplification in neuroblastoma: a SIOP Europe Neuroblastoma Study

British Journal of Cancer
A P BerbegallI M Ambros

Abstract

In neuroblastoma (NB), the most powerful prognostic marker, the MYCN amplification (MNA), occasionally shows intratumoural heterogeneity (ITH), i.e. coexistence of MYCN-amplified and non-MYCN-amplified tumour cell clones, called heterogeneous MNA (hetMNA). Prognostication and therapy allocation are still unsolved issues. The SIOPEN Biology group analysed 99 hetMNA NBs focussing on the prognostic significance of MYCN ITH. Patients <18 months (18 m) showed a better outcome in all stages as compared to older patients (5-year OS in localised stages: <18 m: 0.95 ± 0.04, >18 m: 0.67 ± 0.14, p = 0.011; metastatic: <18 m: 0.76 ± 0.15, >18 m: 0.28 ± 0.09, p = 0.084). The genomic 'background', but not MNA clone sizes, correlated significantly with relapse frequency and OS. No relapses occurred in cases of only numerical chromosomal aberrations. Infiltrated bone marrows and relapse tumour cells mostly displayed no MNA. However, one stage 4s tumour with segmental chromosomal aberrations showed a homogeneous MNA in the relapse. This study provides a rationale for the necessary distinction between heterogeneous and homogeneous MNA. HetMNA tumours have to be evaluated individually, taking age, stage and, most importantly, genomic background i...Continue Reading

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Citations

May 17, 2019·Journal of Pediatric Hematology/oncology·Karin P S Langenberg-VervergaertDaniel A Morgenstern
Jul 26, 2019·Journal of Clinical Laboratory Analysis·Xiaokai HuangHaixia Zhou
Nov 22, 2019·Genes, Chromosomes & Cancer·Kai DuanCatherine T Chung
May 19, 2021·Pediatric Blood & Cancer·Angela Di GiannataleLuca Boldrini
Jun 12, 2021·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Angela BelliniGudrun Schleiermacher

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Methods Mentioned

BETA
Fluorescence
flow cytometry
chromosomal aberrations
PCR

Clinical Trials Mentioned

NCT01728155

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