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Childhood Malignancies, Cysts, and Sinuses of the Head and Neck
Published in R James A England, Eamon Shamil, Rajeev Mathew, Manohar Bance, Pavol Surda, Jemy Jose, Omar Hilmi, Adam J Donne, Scott-Brown's Essential Otorhinolaryngology, 2022
Treatment is patient-dependent: Curative surgery for localized cervical neuroblastoma.Multiagent chemotherapy if incomplete resection, amplification of MYCN proto-oncogene, or distant metastases.Many tumours are radiosensitive.
Neuroblastoma
Published in Prem Puri, Newborn Surgery, 2017
Overall, approximately 25% of primary neuroblastomas have MYCN amplification, being present in 40% with advanced disease but only 5%–10% with low-stage disease.11 The copy number, which can range from 5- to 500-fold amplification, is usually consistent among primary and metastatic sites and at different times during tumor evolution and treatment. This finding suggests that MYCN amplification is an early event in the pathogenesis of neuroblastoma. Amplification of MYCN is associated with advanced stages of disease, rapid tumor progression, and poor outcome; therefore, it is a powerful prognostic indicator of biologically aggressive tumor behavior.11,12
Paediatric oncology
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2014
Stephen Lowis, Rachel Cox, John Moppett, Antony Ng
Disease stage, patient age and certain biological variables are all important clinical prognostic factors. MYCN amplification is well recognized as an adverse prognostic feature for both lower-stage tumour and disseminated disease.130–132 Gain of chromosome 17q133 and loss of 1p and 11q are also associated with an adverse outcome.134 Therefore, segmental rather than numerical chromosomal aberrations in tumour carry an unfavourable prognosis and higher risk of relapse, although some of these segmental aberrations (such as 17q+ and 1p+) require further prospective studies by the INRG to establish a consensus view on prognostic significance.130,135
Macrophage infiltration promotes regrowth in MYCN-amplified neuroblastoma after chemotherapy
Published in OncoImmunology, 2023
Anders Valind, Bronte Manouk Verhoeven, Jens Enoksson, Jenny Karlsson, Gustav Christensson, Adriana Mañas, Kristina Aaltonen, Caroline Jansson, Daniel Bexell, Ninib Baryawno, David Gisselsson, Catharina Hagerling
Neuroblastoma is a pediatric solid tumor that arises from the sympathetic nervous system and presents with a mass in the adrenal gland or along the sympathetic chain.1 It is the most common extracranial solid tumor in children accounting for 6–10% of pediatric cancers.2,3 Despite advances in risk stratification and therapy, neuroblastoma remains a therapeutic challenge, accounting for approximately 15% of all pediatric cancer deaths.4–6 Neuroblastoma is stratified into low-, intermediate- or high-risk groups, according to the International Neuroblastoma Risk Group (INRG) consensus criteria, which include age at diagnosis, histological category, and genetic characteristics such as MYCN amplification (MNA+).7 MNA+ is found in approximately 20% of all neuroblastoma patients and accounts for 40% of all high-risk neuroblastoma cases.8 Increased expression of MYCN is a tumor-initiating event responsible for the development of high-risk neuroblastoma.9,10 Besides having a direct effect on neuroblastoma development, MNA+ induces an immunosuppressive tumor microenvironment. MYCN negatively regulates ligands for natural killer (NK) receptors, and MNA+ is associated with the downregulation of MHC-I expression in neuroblastoma, rendering tumor cells less susceptible to recognition and killing by NK- and T-cells.11–13 Moreover, MNA-positivity correlates with the infiltration of tumor-associated macrophages (TAMs) into neuroblastoma tumors.13,14
Targeting the DNA damage response in pediatric malignancies
Published in Expert Review of Anticancer Therapy, 2022
Jenna M Gedminas, Theodore W Laetsch
The MYC family of proto-oncogenes are transcription factors that mediate the transcription of multiple genes include some involved in DNA repair [88]. Amplification of MYCN is present in approximately 25% of patients with neuroblastoma and is independently associated with a poor prognosis [89]. Over-expression of MYCN has been shown to drive cell proliferation with a rapid progression through S-phase [90,91]. Importantly, MYCN amplified tumors have increased levels of expression of genes involved in cell cycle checkpoints and DNA repair pathways including ATR, CHK1, and PARP1/2, as well as increased levels of endogenous replication stress [91–93]. Rapid cell cycle progression and increased expression of these pathways are associated with increased replication stress and an increased reliance on DNA repair [90,91,94]. Consistent with this, King, et al. have shown that inhibition of ATR in MYCN expressing neuroblastoma cells results in increased levels on replication stress compared to cells in which MYCN is turned off [95]. In addition to inhibition of the ATR pathway, there is also preclinical evidence for using a combination of CHK1 and PARP inhibition to inhibit cell proliferation in vitro and in vivo in MYCN amplified neuroblastoma [93]. These effects were seen regardless of ATM status [93].
Early Decline of Neuron-Specific Enolase during Neuroblastoma Chemotherapy is a Predictive Factor of Clinical Outcome
Published in Pediatric Hematology and Oncology, 2021
Fu-Yi Zhu, Jie Yan, Yan-Na Cao, Yan Jin, Jie Li, Qiang Zhao
Another study reported that serum NSE correlated with NB tumor volume and tumor-related death. Kleopatra’s research discovered that serum NSE correlates to NB tumor burden and has a linear correlation with maximum tumor diameter.15 Won Lee and his group observed patients with MYCN amplification have a better response to treatment, which is mainly shown in the remarkable reduction of primary tumor volume after 3 cycles of chemotherapy and the rapid decline of serum NSE levels.16 In our study, for the change of primary tumor, despite the absence of a statistically significant difference in serum NSE levels between PR and SD after 3 chemotherapy cycles, we noted a trend that patients with PR had lower NSE levels than those with SD. Recent research showed that cfDNA from plasma can be used to evaluate early changes in tumor burden and response to treatment.17 It has been observed that during early chemotherapy, most NB patients respond well, and cfDNA and NSE are down regulated more in NB patients with PR than in those with SD. The cfDNA levels are remarkably comparable between PR and SD only at CC4 stage. Analysis of the maintenance stage response rate revealed the further decline in cfDNA levels. Concurrently, a similar tendency was observed in the change of serum NSE levels.