Implementation of the plasma MYCN/NAGK ratio to detect MYCN amplification in patients with neuroblastoma

Su, Yan; Wang, Lijun; Zhao, Qian; Yue, Zhixia; Zhao, Wen; Wang, Xisi; Duan, Chao; Jin, Mei; Zhang, Dawei; Chen, Shenglan; Yin, Junhui; Qiu, Lihua; Cheng, Xiaoxing; Xu, Zhenhe; Ma, Xiaoli

doi:10.1002/1878-0261.12794

Cited by 6 publications

(5 citation statements)

References 46 publications

(87 reference statements)

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“…Our study considered the status of MYCN, 11q23 and 1p36 LOH. They were present in 16.2%, 30.5% and 33.1% of patients, respectively, which was consistent with previous reports 13,22 . Here, we found that only one patient presented with both MYCN amplification and 11q23 LOH.…”

Section: Discussionsupporting

confidence: 93%

“…They were present in 16.2%, 30.5% and 33.1% of patients, respectively, which was consistent with previous reports. 13,22 Here, we found that only one patient presented with both MYCN amplification and 11q23 LOH. The two markers were negatively correlated, as reported.…”

Section: Discussionmentioning

confidence: 66%

“…The patients were diagnosed according to the International Neuroblastoma Risk Group Staging System (INRGSS) 12 and treated with the BCH‐NB‐2007 protocol (based on the Hong Kong Paediatric Haematology and Oncology Study Group guidelines and the results of a study in Germany) . 13 All patients had received multidisciplinary treatment according to risk stratification. After that, the patients were monitored and evaluated every 3 months.…”

Section: Methodsmentioning

confidence: 99%

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MYCN amplification plus 1p36 loss of heterozygosity predicts ultra high risk in bone marrow metastatic neuroblastoma

et al. 2022

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Background This study aimed to better understand the prognostic effect of multiple genetic markers and identify more subpopulations at ultra high risk of poor outcome in bone marrow (BM) metastatic neuroblastoma (NB). Methods We screened the MYCN, 1p36 and 11q23 loss of heterozygosity (LOH) statuses of 154 patients by interphase fluorescence in situ hybridization of BM cells. The clinical characteristics of patients with the three markers and their associations with prognosis were analysed. Results MYCN amplification and LOH at 1p36 and 11q23 were identified in 16.2%, 33.1% and 30.5% of patients, respectively. There were strong associations between MYCN amplification and 1p36 LOH as well as 11q23 LOH. Both MYCN amplification and 1p36 LOH were strongly associated with high levels of lactate dehydrogenase (LDH) and neuron‐specific enolase, more than 3 metastatic organs, and more events. 11q23 LOH occurred mainly in patients older than 18 months, and those who had high LDH levels. In univariate analysis, patients with MYCN amplification had poorer prognosis than those without. Patients with 1p36 LOH had a 3‐year event‐free survival (EFS) and overall survival lower than those without. 11q23 LOH was associated with poorer EFS only for patients without MYCN amplification. In a multivariate model, MYCN amplification was independently associated with decreased EFS in all cohorts. 11q23 LOH was an independent prognostic factor for patients without MYCN amplification, whereas 1p36 LOH was not an independent marker regardless of MYCN amplification. Compared with all cohorts, patients with both MYCN amplification and 1p36 LOH had the worst outcome and clinical features. Conclusions Patients with both MYCN amplification and 1p36LOH had the worst survival rate, indicating an ultra high‐risk group. Our results may be applied in clinical practice for accurate risk stratification in future studies.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 66%

Section: Methodsmentioning

confidence: 99%

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MYCN amplification plus 1p36 loss of heterozygosity predicts ultra high risk in bone marrow metastatic neuroblastoma

et al. 2022

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“…Neuroblastoma (NB) is the most frequent extracranial solid tumor, which arises from neural crest cells of sympathetic nervous system 1 . It represents 8%–10% of all pediatric tumors and up to 15.84% in infants, but accounts for 10%–15% of cancer‐related deaths in children 2,3 .…”

Section: Introductionmentioning

confidence: 99%

Combined analysis of PHOX2B at two time points and its value for further risk stratification in high‐risk neuroblastoma

Yue

Gao

Xing

et al. 2023

Pediatric Blood & Cancer

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Background Risk stratification of high‐risk neuroblastoma (NB) is crucial for exploring treatments. This study aimed to explore the value of minimal residual disease (MRD) based on PHOX2B levels for further risk stratification in high‐risk NB. Methods The expression of PHOX2B was monitored at two time points (after two and six cycles of induction chemotherapy, TP1 and TP2, respectively) by real‐time polymerase chain reaction (RT‐PCR). The clinical characteristics between groups and survival rates were analyzed. Results The study included 151 high‐risk patients. Positive expression of PHOX2B at diagnosis was seen in 129 cases. PHOX2B was mainly expressed in patients with high lactate dehydrogenase (LDH) and neuron‐specific enolase (NSE) levels (p < .001), bone marrow metastasis (p < .001), more than three metastatic organs (p < .001), 11q23 loss of heterozygosity (LOH) (p = .007), and when more events occurred (p = .012). The 4‐year EFS rate was significantly lower in patients with positive PHOX2B expression compared to the negative group at diagnosis (32.9% ± 6.2% vs. 74.5% ± 10.1%, p = .005). We stratified the 151 patients into three MRD risk groups: low high‐risk (low‐HR), with TP1 less than 10−4 and TP2 less than 10−4; ultra‐HR, with TP1 greater than or equal to 10−2 or TP2 greater than or equal to 10−4, and others classified as intermediate‐HR. Patients in ultra‐HR had the worst survival rate compared with other two groups (p = .02). In a multivariate model, MRD risk stratification based on PHOX2B levels at TP1 and TP2 was an independent prognostic factor for high‐risk patients (p = .001). Patients in ultra‐HR were associated with 11q23 LOH (p < .001), more than three organs of metastasis (p = .005), bone marrow metastasis (p < .001), and occurrence of more events (p = .009). Conclusions MRD risk stratification based on PHOX2B levels at two time points (after two and six cycles of induction chemotherapy) provided a stratification system for high‐risk NB, which successfully predicted treatment outcomes. Our results present an effective method for further stratification of high‐risk NB.

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“…Neuroblastoma (NB) is one of the most common malignant tumors in children, which originates from neural-crest cells, and related with about 12% to 15% of pediatric cancer deaths [ 1 , 2 ]. Approximately 50% of NB patients show extensive metastases at initial diagnosis, which would have a poor prognosis [ 3 , 4 ]. Bone marrow is the most common metastasis site of NB, and patients without bone marrow involvement (BMI) would have a more favorable prognosis than those with BMI [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

The Diagnostic Value of 18F-FDG PET/CT Bone Marrow Uptake Pattern in Detecting Bone Marrow Involvement in Pediatric Neuroblastoma Patients

Liu

Yang

et al. 2022

Contrast Media & Molecular Imaging

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Objectives. To explore the diagnostic value of 18F-FDG PET/CT bone marrow uptake pattern (BMUP) in detecting bone marrow involvement (BMI) in pediatric neuroblastoma (NB) patients. Methods. Ninety-eight NB patients were enrolled in BMI analysis. Four patterns of bone marrow uptake were categorized based on pretreatment cF-FDG PET/CT images. Some crucial inspection indexes and 18F-FDG PET/CT metabolic parameters were analyzed. The BMUP was divided into BMUP1, BMUP2, BMUP3, and BMUP4. Paired-like homeobox 2b (PHOX2B) of bone marrow and blood, bone marrow biopsy (BMB) result, and 18F-FDG PET/CT were compared to detect BMI. All patients were followed up for at least six months. Results. BMUP had excellent consistency among different physicians. Kappa coefficients of two residents and two attending physicians and between the resident and attending physician, were 0.857, 0.891, and 0.845, respectively. The optimal cut-off value of SUVmax-Bone/Liver was 2.08 to diagnose BMI for BMUP3 patients, and the area under curve (AUC) was 0.873. AUC of PHOX2B of bone marrow (PHOX2B of BM), PHOX2B of blood, BMB, and 18F-FDG PET/CT were 0.916, 0.811, 0.806, and 0.904, respectively. There was no significant difference between PHOX2B of BM and PET/CT. Positive predictive value, negative predictive value, sensitivity, and specificity in diagnosis of BMI were 92.9%, 92.9%, 97.0%, and 83.9% for PET/CT and 96.7%, 80.6%, 89.6%, and 93.5% for PHOX2B of BM, respectively. Conclusions. BMUP of pretreatment 18F-FDG PET/CT is a simple and practical method, which has a relatively high diagnostic efficiency in detecting BMI and might decrease unnecessary invasive inspections in some pediatric NB patients.

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Implementation of the plasma MYCN/NAGK ratio to detect MYCN amplification in patients with neuroblastoma

Cited by 6 publications

References 46 publications

MYCN amplification plus 1p36 loss of heterozygosity predicts ultra high risk in bone marrow metastatic neuroblastoma

MYCN amplification plus 1p36 loss of heterozygosity predicts ultra high risk in bone marrow metastatic neuroblastoma

Combined analysis of PHOX2B at two time points and its value for further risk stratification in high‐risk neuroblastoma

The Diagnostic Value of 18F-FDG PET/CT Bone Marrow Uptake Pattern in Detecting Bone Marrow Involvement in Pediatric Neuroblastoma Patients

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