AI Article Synopsis
- MYCN amplification (MNA) in neuroblastoma (NB) can exhibit intratumoural heterogeneity (ITH), with both MNA and non-MNA cell clones present, affecting treatment decisions and outcomes.
- A study of 99 cases with heterogeneous MNA found that younger patients (<18 months) had significantly better survival rates compared to older patients, regardless of disease stage, indicating age plays a crucial role in prognosis.
- It’s important to differentiate between heterogeneous and homogeneous MNA in tumors, as individual assessment based on age, disease stage, and genomic characteristics can help prevent overtreatment, especially in infants.
Article Abstract
Background: 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.
Methods: The SIOPEN Biology group analysed 99 hetMNA NBs focussing on the prognostic significance of MYCN ITH.
Results: 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.
Conclusions: 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 into account to avoid unnecessary upgrading of risk/overtreatment, especially in infants, as well as in order to identify tumours prone to developing homogeneous MNA.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988829 | PMC |
| http://dx.doi.org/10.1038/s41416-018-0098-6 | DOI Listing |
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