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Chromosome band 11q23 deletion predicts poor prognosis in bone marrow metastatic neuroblastoma patients without MYCN amplification

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机构: [1]Capital Med Univ, Beijing Key Lab Pediat Hematol Oncol,Natl Ctr Chi, Natl Key Discipline Pediat,Beijing Childrens Hosp, Minist Educ,MOE Key Lab Major Dis Children,Hemato, 56 Nanlishi Rd, Beijing 100045, Peoples R China
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关键词: Neuroblastoma MYCN amplification 11q23 deletion Fluorescence in situ hybridization Bone marrow metastasis Event-free survival Overall survival Neuron-specific enolase Lactate dehydrogenase

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Background Interphase fluorescence in situ hybridization (FISH) of bone marrow cells has been confirmed to be a direct and valid method to assess the v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) amplification in patients with bone marrow metastatic neuroblastoma. MYCN amplification alone, however, is insufficient for pretreatment risk stratification. Chromosome band 11q23 deletion has recently been included in the risk stratification of neuroblastoma. In the present study, we aimed to evaluate the biological characteristics and prognostic impact of 11q23 deletion and MYCN amplification in patients with bone marrow metastatic neuroblastoma. Methods We analyzed the MYCN and 11q23 statuses of 101 patients with bone marrow metastatic neuroblastoma using interphase FISH of bone marrow cells. We specifically compared the biological characteristics and prognostic impact of both aberrations. Results MYCN amplification and 11q23 deletion were seen in 12 (11.9%) and 40 (39.6%) patients. The two markers were mutually exclusive. MYCN amplification occurred mainly in patients with high lactate dehydrogenase (LDH) and high neuron-specific enolase (NSE) levels (both P < 0.001), and MYCN-amplified patients had more events (tumor relapse, progression, or death) than MYCN-normal patients (P = 0.004). 11q23 deletion was associated only with age (P = 0.001). Patients with MYCN amplification had poorer outcomes than those with normal MYCN (3-year event-free survival [EFS] rate: 8.3 +/- 8.0% vs. 43.8 +/- 8.5%, P < 0.001; 3-year overall survival [OS] rate: 10.4 +/- 9.7% vs. 63.5% +/- 5.7%, P < 0.001). 11q23 deletion reflected a poor prognosis only for patients with normal MYCN (3-year EFS rate: 34.3 +/- 9.5% vs. 53.4 +/- 10.3%, P = 0.037; 3-year OS rate: 42.9 +/- 10.4% vs. 75.9 +/- 6.1%, P = 0.048). Those with both MYCN amplification and 11q23 deletion had the worst outcome (P < 0.001). Conclusions Chromosome band 11q23 deletion predicts poor prognosis only in bone marrow metastatic neuroblastoma patients without MYCN amplification. Combined assessment of the two markers was much superior to single-marker assessment in recognizing the patients at a high risk of disease progression.

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大类 | 1 区 医学
小类 | 2 区 肿瘤学
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Q1 ONCOLOGY

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第一作者机构: [1]Capital Med Univ, Beijing Key Lab Pediat Hematol Oncol,Natl Ctr Chi, Natl Key Discipline Pediat,Beijing Childrens Hosp, Minist Educ,MOE Key Lab Major Dis Children,Hemato, 56 Nanlishi Rd, Beijing 100045, Peoples R China
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通讯机构: [1]Capital Med Univ, Beijing Key Lab Pediat Hematol Oncol,Natl Ctr Chi, Natl Key Discipline Pediat,Beijing Childrens Hosp, Minist Educ,MOE Key Lab Major Dis Children,Hemato, 56 Nanlishi Rd, Beijing 100045, Peoples R China
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