Deciphering the first steps of follicular lymphomagenesis: a comprehensive genetic analysis of follicular lymphoma in situ (in situ follicular neoplasia) and its progression

滤泡性淋巴瘤（FL）是西方世界最常见的惰性恶性淋巴瘤。在组织中可识别的第一个前体阶段是所谓的滤泡性原位淋巴瘤（FLIS）。它的特点是抗凋亡蛋白BCL-2在正常淋巴结的双生殖中心强烈过表达，尽管它已经带有滤泡性淋巴瘤的遗传标志，即易位t，但与临床无关（14;18）。由于FLIS仅显示出较低的进展风险，因此需要额外的遗传改变才能发展为显性疾病。我们项目的目标是利用最先进的分子技术，全面表征FLIS的遗传改变及其在进展到明显淋巴瘤过程中的演变。该项目将通过描述驱动癌前t(14;18)+细胞进入临床淋巴瘤的关键分子事件，更好地了解FL的早期发病机制。

Follicular lymphoma (FL) is the most common indolent malignant lymphoma in the Western world. The first precursor stage identifiable in tissues is the so-called follicular lymphoma in situ (FLIS). It is characterized by strong overexpression of the anti-apoptotic protein BCL-2 in geminal centers of otherwise normal lymph nodes and is of no clinical relevance, although it already carries the genetic hallmark of follicular lymphoma, namely the translocation t(14;18). Since FLIS shows only low risk for progression, additional genetic alterations are required for the development of manifest disease. Goal of our project ist a comprehensive characterization of genetic alterations in FLIS and their evolution during progression to manifest lymphoma, using state of the art molecular techniques. The project shall provide better understanding of early FL pathogenesis through describing key molecular events driving premalignant t(14;18)+ cells into clinical lymphoma.