2017-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/683393摘要：神經母細胞瘤（neuroblastoma；簡稱NB）是發源於交感神經系統的胚胎型腫瘤，為兒童最常見的顱外固態腫瘤。治療預後與發病年齡、疾病期別和基因體型別有關，而且差異很大：有一群在嬰兒期發病，預後很好，甚至腫瘤可以自行縮小消失；有一些在兒童期發病之局部腫瘤，帶有好的基因體型別，只須接受輕度的化學治療，即可有不錯的預後；但也有在兒童期發病時已轉移之高度惡性腫瘤，帶有不好的基因體型別，即使經過手術、化療、自體骨髓移植、放射線治療，其存活率仍甚差，且需承受治療相關的諸多副作用。神經母細胞瘤的基因體型別不僅與治療預後相關，同時也代表可能有新的標靶藥物以進行精準治療。臺大醫院近七成的病童於診斷時已是多處轉移的第四期疾病，目前使用螢光原位雜合技術、染色體晶片分析(Array CGH)來檢測MYCN 基因放大、或染色體特定位置節段性數量變化等基因體型別，但對於其他基因體型別變化：如基因突變、基因轉位、基因套數變化等都無法檢測。本研究計畫建立神經母細胞瘤檢測平台，利用流式細胞儀、聚合酶連鎖反應（polymerase chain reaction,PCR）或次世代定序儀（next generation sequencing, NGS）等方法，檢測神經母細胞瘤患者手術剩餘檢體、骨髓檢體中的基因體型別變化，對神經母細胞瘤進行全面性的研究，希望能找到更精確的預後因子，以幫助病童進行適當治療；檢測特殊基因體型別，找出可使用標靶藥物進行精準治療；發展液態生物檢體(liquid biopsy) 診斷和微量殘存腫瘤檢測技術，即時診斷和評估治療效果。<br> Abstract: Neuroblastoma (NB) originates from the sympathetic nervous system and is themost common extracranial solid tumor in children. NB occurs in very youngchildren, with a median age of 17 months at diagnosis. The prognosis are poor inthe neuroblastoma. Although neuroblastoma constitutes only about 5% of allpediatric cancers, it causes up to 10% of childhood cancer mortality. A hallmark ofNB is its heterogeneity in clinical presentation, course and prognosis, range frominfants with multiple tumors that can spontaneously regress; to children who havelocalized tumors with favorable genomic types and excellent overall survival withlimited cytotoxic chemotherapy; to critical ill older children, adolescents withwidespread metastasis disease that can grow relentless despite intensive multimodaltherapy: chemotherapy, surgery, autologous stem cell transplantation, radiationtherapy, and differentiation therapy. Genomic characteristics not only has catalyzedthe prognosis, but also has revealed novel therapeutic targets. In our hospital, nearly70% of patients with NB presented high-risk features. Currently we detect onlyMYCN oncogene, or segmental chromosomal alterations by in situ hybridizationand array CGH. But the specific gene mutation (ex. ALK, ATRX), translocationand DNA ploidy cannot be detected. Our study is planned to set up theneuroblastoma genomic diagnostic platform to detect chromosome change, specificgene change (amplification, deletetion, mutatation, translocation), and DNA ploidyby PCR, target sequencing, flow cytometry methods. The study aim to identify riskgroup, detect drugable targets (e.g. ALK inhibitor) and detect minimal residual tumor.IL-6peptide drug