Genomic biomarkers of splenic lymphoma

项目总结 脾淋巴瘤的基因组生物标志物 脾边缘带淋巴瘤(SMZL)是脾内最常见的原发肿瘤。SMZL 通常在发病时涉及骨髓和外周血(PB)。诊断结果总是 在疾病的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，因为没有特殊的组织病理学或 疾病的免疫组织化学生物标志物。因此，SMZL的早期诊断是具有挑战性的 在大多数临床情况下都不能实现。此外，SMZL是诊断重复性最差的类别之一 淋巴瘤的症状。次优的诊断准确率需要发展定性和客观 SMZL的生物标志物。重要的是，虽然所有SMZL病例在诊断时都有PB受累， 然而，这种生物学特征还没有被用来可靠地早期发现疾病。vbl.使用 全基因组和外显子组测序，我们和其他人定义了SMZL的基因组图谱并鉴定了 SMZL中反复突变基因。一个尚未得到满足的临床需求是开发可靠的生物标记物 根据SMZL特有的基因组改变，对该病进行早期准确的诊断。我们 在本申请中建议开发一种基于基因组的方法，利用并验证外周血为 以便对疾病进行早期和准确的诊断。应用程序的总体影响是建立一个 通过分析外周血进行早期、敏感和准确的疾病诊断范例，从而 允许对这种疾病进行早期和适当的治疗。

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.