Clinical Cancer Cytogenetics

NCI/CCR/LP临床细胞遗传学科的任务是为Mark O.Hatfield临床研究中心评估和治疗的患者提供最先进的诊断服务；进行临床转化性癌症细胞遗传学研究；并在临床细胞遗传学服务和研究的原则和实践方面向学生、住院医生和研究员提供教学和指导。这个项目占该部门工作的80%，其目标是提供诊断服务和对NCI和其他研究所医生根据临床研究方案输入的患者样本进行研究测试，就NCI临床转化研究方案进行合作，并对学生、住院医生和研究员进行教学和指导。临床细胞遗传学部门是NIH唯一提供细胞遗传学诊断服务的内部实验室。该实验室由美国病理学家学会、医院联合认可委员会和1988年临床实验室改进法案进行检查和认证。我们目前对来自几个机构(NCI、NIAID、NICHD)和临床中心实验室医学部的患者样本进行高度复杂的常规和分子细胞遗传学检测。在超过80%的病例中，检测是针对癌前和恶性疾病中的获得性染色体异常，在其余病例中是针对结构性染色体异常。我们的测试结果用于患者的诊断、分类、预后和治疗计划。他们还提供了可能对肿瘤的发生和发展起重要作用的基因区域的关键信息，从而为进一步的恶性肿瘤分子生物学研究提供了起点。该小组成员正在对进入NCI临床研究方案的患者进行常规诊断和研究，包括荧光原位杂交(FISH)、比较基因组杂交(CGH)和光谱核型分析(SKY)。Arthur博士是以下七个活跃方案的副研究员：a.97-C-0178“氟达拉滨治疗慢性淋巴细胞性白血病(CLL)：cDNA微阵列基因表达分析和临床前骨髓移植/免疫疗法研究”，PI：Wyndham Wilson，M.D.，Ph.D.B.01-C-0125：“非清髓性、人类白细胞抗原相合的异基因干细胞移植治疗儿童恶性血液病的初步研究”，PI：Alan S.Wayne，M.D.C.。02-C-0052“遗传性骨髓衰竭综合征中癌症易感性的病因学研究”，PI：Blanche Alter，M.D.M.P.H.D.04-C-0079“BL22治疗难治性CD22阳性白血病和淋巴瘤的儿科I期试验”，PI：Alan S.Wayne，M.D.E.04-C-0102《血液恶性生物学研究》，PI：Alan S.Wayne，M.D.F.04-C-0168“LMB-2治疗难治性CD25阳性白血病和淋巴瘤的儿科I期试验”，PI：Alan S.Wayne，M.D.G.04-C-0095“重症系统性红斑狼疮患者强化淋巴滤除和自体造血干细胞移植的初步研究”，PI：Steven Z.Pavletic，M.D.作为这些研究的一部分产生的细胞遗传学数据对患者的诊断、分类和治疗计划是有用的。它们对于监测患者对实验性治疗的反应以及与其他研究研究的相关性也很重要。它们有可能发现这些疾病之间的新的临床病理联系，以及可能成为未来治疗目标的生物学机制。最后，在临床细胞遗传学服务和研究的原则和实践方面，分部成员教授和指导学生、住院医生和研究员。除了指导三名暑期学生和两名博士后研究员外，Arthur博士还是NCI/CCR/LP住院医生、NCI/CCR/LP血液病理学研究员和NHGRI临床细胞遗传学Fe的成员

The mission of the NCI/CCR/LP Clinical Cytogenetics Section is to provide state-of-the-art diagnostic services for patients evaluated and treated at the Mark O. Hatfield Clinical Research Center; to perform clinical translational cancer cytogenetics research; and to teach and mentor students, residents, and fellows in the principles and practices of clinical cytogenetics service and research. The goals of this project, which comprises 80 percent of the effort of the section, are to provide diagnostic service and research testing on samples from patients entered on clinical research protocols by NCI and other Institute physicians, to collaborate on NCI clinical translational research protocols, and to teach and mentor students, residents, and fellows.The Clinical Cytogenetics Section is the only intramural NIH laboratory performing cytogenetics diagnostic services. The laboratory is inspected and certified by the College of American Pathologists, the Joint Commission for Accreditation of Hospitals, and the Clinical Laboratory Improvement Act of 1988. We currently perform highly complex routine and molecular cytogenetic testing on patient samples from several institutes (NCI, NIAID, NICHD) and the Clinical Center Department of Laboratory Medicine. In greater than 80 percent of cases the testing is for acquired chromosome abnormalities in premalignant and malignant disorders, and in the remaining cases is for constitutional chromosome abnormalities. The results of our testing are used for diagnosis, classification, prognosis, and treatment planning for patients. They also provide critical information regarding the gene regions that may be important for tumor initiation and progression, and thus serve as a starting point for further molecular biologic investigations of malignant diseases.Section members are conducting routine diagnostic and research fluorescence in-situ hybridization (FISH), comparative genomic hybridization (CGH), and spectral karyotyping (SKY) analyses of patients entered on NCI clinical research protocols. Dr. Arthur is an Associate Investigator on seven active protocols as follows:a. 97-C-0178 "Fludarabine Treatment of Chronic Lymphocytic Leukemia (CLL): cDNA Microarray Gene Expression Analysis, and Pre-Clinical Bone Marrow Transplant/ Immunotherapy Studies," PI: Wyndham Wilson, M.D., Ph.D. b. 01-C-0125 "Pilot Study of Non-myeloablative, HLA-matched Allogeneic Stem Cell Transplantation for Pediatric Hematopoietic Malignancies," PI: Alan S. Wayne, M.D.c. 02-C-0052 "Etiologic Investigation of Cancer Susceptibility in Inherited Bone Marrow Failure Syndromes," PI: Blanche Alter, M.D. M.P.H. d. 04-C-0079 "Pediatric Phase I Trial of BL22 for Refractory CD22-Positive Leukemias and Lymphomas," PI: Alan S. Wayne, M.D.e. 04-C-0102 "Hematologic Malignancy Biology Study," PI: Alan S. Wayne, M.D.f. 04-C-0168 "Pediatric Phase I Trial of LMB-2 for Refractory CD25-Positive Leukemias and Lymphomas," PI: Alan S. Wayne, M.D.g. 04-C-0095 "A Pilot Study of Intensified Lymphodepletion Followed by Autologous Hematopoietic Stem Cell Transplantation in Patients with Severe Systemic Lupus Erythematosus," PI: Steven Z. Pavletic, M.D.The cytogenetics data generated as part of these studies are clinically useful for diagnosis, classification, and treatment planning for patients. They are also important for monitoring patient response to experimental treatment, and for correlation with other research studies. They have the potential for discovery of new clinical-pathological associations among these diseases and of biological mechanisms that may be targeted with future therapies. Finally, section members teach and mentor students, residents, and fellows in the principles and practices of clinical cytogenetics service and research. In addition to mentoring three summer students and two postdoctoral fellows, Dr. Arthur is a member of the NCI/CCR/LP Resident, NCI/CCR/LP Hematopathology Fellow, and NHGRI Clinical Cytogenetics Fe