GENETIC MECHANISMS OF B CELL LYMPHOMA

本计划项目的目标是深入分析正常和 我们最近从IG中克隆的两个新基因的功能失调 弥漫性淋巴瘤伴大淋巴结转移的基因相关染色体易位 细胞成分（DLLC），临床上最重要的NHL形式。 一、 BCL 6是定位于染色体带的锌指转录因子 3q27。 BCL 6通过其5'非编码区的重排而改变， 约30%的DLLC和约50%的滤泡性淋巴瘤（FL）。 最近 研究表明，在约70%的DLLC和约50%的FL中，BCL 6 一个基因也会被多个，通常是双等位基因的突变簇所改变 在其非编码区中。 这些突变起源于体细胞， 不依赖于染色体易位重排。 我们的目标 BCL 6研究由本计划项目中的三个项目代表 主要探讨了以下几个问题：（1）机制、后果和作用 在NHL发展中BCL 6和细胞因子信号传导，和（3）POK蛋白 在个体发育、淋巴细胞生成和淋巴瘤发生中。 BCL 8刚刚被 通过在DLLC中与IGH基因的重排， 染色体易位 它映射到15 q11 -13。 的目标 本项目的最后一个项目是研究结构和 正常人BCL-8的功能及其机制和后果 改变NHL的发展。 这些研究旨在获得 了解BCL 6和BCL 8基因的正常和异常功能。 这些见解对于理解这些基因在以下方面的作用至关重要： 正常哺乳动物发育和人类肿瘤发生。 这四个项目 将由行政核心和小鼠分子病理学 核心

The goal of this Program Project is in-depth analysis of normal and deregulated function of two novel genes recently cloned by us from IG gene-associated chromosome translocations in diffuse lymphoma with a large cell component (DLLC), clinically the most significant form of NHL. One, BCL6, is a zinc finger transcription factor mapped to chromosome band 3q27. BCL6 is altered by rearrangement in its 5' non-coding region in about 30% of DLLC and about 50% of follicular lymphomas (FL). Recent studies showed that in about 70% of DLLC and about 50% of FL, the BCL6 gene is also altered by multiple, often bi-allelic, mutations clustering in its %' non-coding region. These mutations are somatic in origin and independent of rearrangement by chromosome translocation. Our goals for BCL6 studies are represented by three projects in this Program Project which address the following issues: (1) mechanism, consequence, and role in NHL development of BCL6 and cytokine signaling, and (3) POK proteins in ontogenesis, lymphopoiesis, and lymphomagenesis. BCL8 has just been identified by virtue of its rearrangement with IGH gene in a DLLC by way of a chromosome translocation. It maps to 15q11-13. The goal of the final project in this Program Project is to investigate the structure and function of normal BCL8 and the mechanism and consequence of its alteration to NHL development. The studies proposed are designed to gain insights into the normal and abnormal function of BCL6 and BCL8 genes. Such insights are essential to understand the roles of these genes in normal mammalian development and human tumorigenesis. The four projects will be aided by an Administrative Core and a Mouse Molecular Pathology Core.