MOLECULAR ANALYSIS OF PEDIATRIC CANCERS

该计划的主要目标是提高灵敏度和特异性 应用免疫组织化学技术诊断小儿常见肿瘤 分子生物学技术 另一个目标是使用儿科 肿瘤标本，以确定分子过程，有助于 儿童实体瘤的恶性表型 儿童常见肿瘤 包括急性淋巴细胞白血病，肾母细胞瘤， 成神经细胞瘤、成神经管细胞瘤、横纹肌肉瘤和成骨肉瘤。 项目1将利用特异性寡核苷酸探针， 白血病克隆的IgH基因座的CDR 3区，以定量 白血病患者骨髓和外周血中白血病细胞的 亚临床疾病 我们将了解到， 的白血病细胞是预测复发后诱导-或期间 维持化疗 项目2描述了肾母细胞瘤锌 指状蛋白在肿瘤样本中通过与特定DNA结合的能力 测序并调节转录。 项目3将确定和 在原始神经外胚层中鉴定NGF诱导的立即早期基因 不能反式激活其他基因的肿瘤， 是终端分化所必需的。 项目4识别和克隆 肺泡上皮细胞t（2;13）易位断裂点特征 横纹肌肉瘤，因为这种易位可能有助于 致瘤性 项目5确定了产生PDGF的骨肉瘤， 了解内源性PDGF的产生是否会导致骨肉瘤生长， 自分泌方式 它还确定了基因和转导机制 在那些对PDGF没有反应的骨肉瘤中受损。

A major goal of this program is to improve the sensitivity and specificity of diagnosis in the common pediatric tumors through application of molecular biological techniques. An additional goal is to use pediatric tumor specimens to define molecular process which contribute to the malignant phenotype of childhood solid tumors. Common childhood tumors that will be studied include acute lymphoblastic leukemia, Wilms tumor, neuroblastoma, medulloblastoma, rhabdomyosarcoma and osteogenic sarcoma. Project 1 will utilize specific oligonucleotide probes, which recognize the CDR3 region of the IgH locus of the leukemic clone, to quantify the number of leukemic cells in the bone marrow and peripheral blood of patients with subclinical disease. It will be learned if the presence of large numbers of leukemic cells are predictive of relapse after induction- or during maintenance-chemotherapy. Project 2 characterizes the Wilms tumor zinc finger protein in tumor samples by the ability to bind to a specific DNA sequence and regulate transcription. Project 3 will identify and characterize NGF induced immediate-early genes in primitive neuroectodermal tumors which are incompetent to trans activity other genes whose expression is required for terminal differentiation. Project 4 identifies and clones the t(2;13) translocation breakpoint characteristic of alveolar rhabdomyosarcoma because this translocation likely contributes to tumorigenicity. Project 5 identifies osteosarcomas which produce PDGF and learns if endogenous PDGF production causes osteosarcomas to grow in an autocrine fashion. It also identifies genes and transduction mechanisms which are impaired in those osteosarcomas which don't respond to PDGF.