Quantitative proteomic analysis of lymphoma transformation

描述(由申请人提供)： 非霍奇金淋巴瘤每年约有50000例新发癌症病例。这一数字的增长超过了大多数其他形式的癌症。在非霍奇金淋巴瘤中，滤泡性淋巴瘤是成人低度恶性B细胞淋巴瘤中最常见的亚型，其临床病程较为缓慢。在相当大比例的病例中，从低级别肿瘤到侵袭性弥漫性大B细胞淋巴瘤有组织学上的转变，中位生存期显著降低。最近出现的复杂的质谱学技术，再加上可以进行瞬时蛋白质鉴定的软件算法，使得研究区分两种生物状态的蛋白质去调节模式成为可能。我们建议结合使用层析技术和串联质谱仪来鉴定伴随着组织转化的蛋白质表达的变化。我们将分析发生在同一个体的滤泡性淋巴瘤和转化的弥漫性大B细胞淋巴瘤的配对队列。相关性：全面识别滤泡性淋巴瘤转化过程中涉及的蛋白质表达的质和量变化，将有助于描绘解除调控的途径，识别不同的转化淋巴瘤预后亚群，并促进针对解除调控途径中的易感因素的新疗法的开发。

DESCRIPTION (provided by applicant): Non-Hodgkin's lymphoma accounts for approximately 50,000 new cases of cancer annually. This figure represents an increase beyond that seen for most other forms of cancer. Among the non-Hodgkin's lymphomas, follicular lymphoma represents the most common subtype of low-grade B-cell lymphoma in adults, and typically pursues an indolent clinical course. In a significant proportion of cases there is histologic transformation from a low-grade neoplasm to an aggressive diffuse large B-cell lymphoma with significantly decreased median survival. The recent advent of sophisticated mass spectrometry technology coupled with software algorithms that permit instantaneous protein identification, makes it feasible to study the pattern of protein deregulation that distinguish two biologic states. We propose to employ a combination of chromatographic techniques and tandem mass spectrometry in the identification of the alterations in protein expression that accompany histologic transformation. We shall be analyzing a cohort of matched pairs of follicular lymphoma and their transformed diffuse large B-cell lymphoma counterparts occurring in the same individual. Relevance: Comprehensive identification of the qualitative and quantitative changes in protein expression that are involved in follicular lymphoma transformation will permit the delineation of deregulated pathways, identify distinct prognostic subgroups of transformed lymphoma, and facilitate the development of novel therapies that target susceptible elements in the deregulated pathways.