Genomic biomarkers of splenic lymphoma

脾淋巴瘤的基因组生物标志物

• 批准号: 10312006
• 负责人: KOJO S. J. ELENITOBA-JOHNSON
• 金额: $ 41.22万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-04 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10312006
• 关键词: Address; B-Lymphocytes; Biologic Characteristic; Biological; Biological Assay; Biological Markers; Blinded; Blood; Blood specimen; Bone Marrow; Bone Marrow Involvement; Categories; Cells; Characteristics; Clinical; Clonality; DNA Sequence Alteration; Detection; Development; Diagnosis; Disease; Early Diagnosis; Future; Gene Mutation; Genes; Genomics; Goals; High-Throughput Nucleotide Sequencing; Immunoglobulin Gene Rearrangement; Immunoglobulin Genes; Lymphoma; Malignant Neoplasms; Modeling; Monitor; Mononuclear; Mutate; Mutation; Mutation Analysis; Mutation Detection; Operative Surgical Procedures; Patients; Performance; Peripheral Blood Involvement; Peripheral Blood Mononuclear Cell; Population; Prospective cohort; Recurrence; Research; Residual Neoplasm; Retrospective cohort; Risk; Sampling; Spleen; Splenectomy; Splenic Tissue; Techniques; Testing; Tissues; Training; Tumor Tissue; accurate diagnosis; base; clinical diagnosis; cohort; diagnostic accuracy; disease diagnosis; early detection biomarkers; exome sequencing; genome sequencing; genomic aberrations; genomic biomarker; immunohistochemical markers; improved; novel; peripheral blood; prospective; virtual; whole genome

PROJECT SUMMARY GENOMIC BIOMARKERS OF SPLENIC LYMPHOMA Splenic marginal zone lymphoma (SMZL) is the most common form of primary cancer in the spleen. SMZL typically involves the bone marrow and peripheral blood (PB) at presentation. The diagnosis is invariably established in late stages of disease via a splenectomy which is a surgical procedure carrying major risk. Additionally, the diagnosis of SMZL is subjective because there are no specific histopathologic or immunohistochemical biomarkers of the disease. Consequently, early diagnosis of SMZL is challenging and not achieved in most clinical scenarios. Further, SMZLs are among the least reproducibly diagnosed category of lymphomas. The suboptimal diagnostic accuracy necessitates the development of qualitative and objective biomarkers of SMZL. Importantly, while all cases of SMZL are characterized by PB involvement at diagnosis, however this biologic feature has not been leveraged for the reliable early detection of the disease. Using whole genome and exome sequencing, we and others defined the genomic landscape of SMZL and identified recurrently mutated genes in SMZL. An unmet clinical need is the development of reliable biomarkers for the early and accurate diagnosis of the disease based on the characteristic genomic alterations of SMZL. We propose in this application to develop a genomic-based approach that utilizes and validates peripheral blood as for early and accurate diagnosis of the disease. The overall impact of the application is the establishment of a paradigm for early, sensitive and accurate disease diagnosis by analysis of peripheral blood, thereby permitting early and appropriate treatment for the disease.

项目摘要 脾淋巴瘤的基因组生物标志物 脾脏边缘区淋巴瘤是脾脏最常见的原发性恶性肿瘤。SMZL 典型地涉及表现时的骨髓和外周血（PB）。诊断结果总是 在疾病晚期通过脾切除术建立，这是一种具有重大风险的外科手术。 此外，SMZL的诊断是主观的，因为没有特异性的组织病理学或病理学特征。 免疫组织化学生物标志物的疾病。因此，SMZL的早期诊断具有挑战性， 在大多数临床情况下无法实现。此外，SMZL是最不可重复诊断的类别之一 淋巴瘤次优的诊断准确性需要定性和客观的发展 SMZL的生物标志物。重要的是，虽然所有SMZL病例的特征都是诊断时PB受累， 然而，这种生物学特征还没有被用于疾病的可靠早期检测。使用 全基因组和外显子组测序，我们和其他人定义了SMZL的基因组景观，并确定了 SMZL中反复突变的基因。一个未满足的临床需求是开发用于肿瘤的可靠生物标志物。 基于SMZL的特征性基因组改变的疾病的早期和准确的诊断。我们 在本申请中，我建议开发一种基于基因组的方法，该方法利用并验证外周血作为 早期和准确的诊断疾病。该申请的总体影响是建立了一个 通过分析外周血进行早期、灵敏和准确的疾病诊断的范例，从而 允许对疾病进行早期和适当的治疗。