BCL-1 REARRANGEMENT IN CENTROCYTIC LYMPHOMA

中心性淋巴瘤是B细胞淋巴瘤的一种生物学亚型 这与11号染色体bcl1重排和PRAD1有关 过度表达。该提案的目标是：1)研究bcl-1 中心性淋巴瘤中的有序重排和易位连接 确定染色体位置、易位位置和核苷酸 易位连接的序列；这将包括括号和 从一些中心性淋巴瘤中分离出易位连接 使用肿瘤基因组DNA文库进行bcl1重排。亚克隆 穿过断点将用于染色体作图和原位 杂交和邻近断裂点的核苷酸序列 将确定bcl1区域，2)进一步剖析bcl1/PRAD1 基因组区域并确定与易位相关的断裂点 PRAD1过表达但bcl1不表达的中心性淋巴瘤 重排；这将需要双向染色体行走 微生物的限制性内切酶图谱和核苷酸序列分析 连接bcl-1区和PRAD1区，从而开发新的DNA探针 可以检测到这个区域的易位断裂点。

Centrocytic lymphoma is a biologically distinct subtype of B-cell lymphoma that has been associated with chromosome 11 bcl-1 rearrangements and PRAD1 overexpression. Objectives of the proposal are: 1) to study the bcl-1 rearrangement and translocation junction in centrocytic lymphoma in order to determine the chromosomal locations, translocation sites and nucleotide sequences of the translocation junction; this will include bracketing and isolating the translocation junction from a number of centrocytic lymphomas with bcl-1 rearrangement using libraries of tumor genomic DNA. Subclones from across the breakpoint will be used for chromosomal mapping and in situ hybridization and the nucleotide sequence of the breakpoint adjacent to the bcl-1 region will be determined, and 2) to further dissect the bcl-1/PRAD1 genomic region and identify translocation-related breakpoints in cases of centrocytic lymphoma that show PRAD1 overexpression but not bcl-1 rearrangements; this will entail bi-directional chromosome walking with restriction enzyme mapping and nucleotide sequence analysis to physically link the bcl-1 region and PRAD1 region, and thus develop new DNA probes that can detect translocation breakpoints in this region.