MOLECULAR ANALYSIS T(11--18)(Q21--Q21)--MALT LYMPHOMA

（改编自研究者摘要）MALT淋巴瘤构成了 最近发现的B细胞非霍奇金淋巴瘤亚型 在粘膜相关淋巴组织（MALT）中，最常见于 胃肠道 这些肿瘤的不寻常特征之一是 特别懒惰的整体过程中，倾向于留在本地， 粘膜部位长时间，以其他能力回家 在传播的早期阶段的粘膜部位， 或依赖于特定的细菌抗原，以及退化或 通过抗生素治疗消除刺激物的细菌来源 y 抗原的 对这些肿瘤的细胞遗传学研究表明， 四分之一的分析病例含有（11;18）（q21;q21）染色体 易位和至少另一个季度有其他畸变， 18号染色体，有时涉及相同的18 q21区域。 研究 本申请中所描述的方法将分析 t（11;18）（q21）断裂点，方法是首先分离 可能还有11号染色体DNA 这些碎片将被 依次用于分离位于或接近 18号和11号染色体上的断裂点 全长cDNA 这些基因的正常版本和这些基因的任何改变形式 将分离由易位产生的DNA， 测定 Southern印迹，荧光原位杂交（FISH），和 将开发t（11;18）（q21;q21）的RT-PCR检测方法，并用于 研究这种易位在组织中的分布和特异性 各种淋巴瘤和增生性淋巴组织。 最后 位于18号染色体上断点附近的基因的功能， 11将通过搜索cDNA序列的同源性来研究， 已知的基因，确定正常组织中的基因， 表达与这些cDNA相对应的基因，并检测其致癌性 由于t（11;18）（q21;21）的改变， 将合适的cDNA构建体插入转基因小鼠中。 结果本组 这些研究将提供深入了解遗传机制， 肿瘤性淋巴细胞的恶性表型 组成MALT淋巴瘤，并可能扩大现有的知识， 正常淋巴细胞代表这些细胞的细胞前体， 肿瘤的

(adapted from the investigator's abstract) MALT lymphomas constitute a recently recognized subtype of B cell non-Hodgkin's lymphomas arising in mucosa-associated lymphoid tissues (MALT), most often in the gastrointestinal tract. Among the unusual features of these tumors is an exceptionally indolent overall course, the tendency to stay localized to mucosal sites for long periods of time, the capacity to home to other mucosal sites during early stages of dissemination, proliferation in respon to or dependent upon specific bacterial antigens, and regression or elimination by antibiotic treatment of the bacterial source of the stimulat y antigen. Cytogenetic studies of these tumors indicate that almost one quarter of the cases analyzed contain a(11;18) (q21;q21) chromosomal translocation and at least another quarter have other aberrations of chromosome 18, sometimes involving the same 18q21 region. Research described in this application will analyze the molecular genetics of the t(11;18) (q21) breakpoint by first isolating genomic fragments of chromosome 18 and possible chromosome 11 DNA. These fragments will be used in turn to isolate fragments of cDNAs for genes lying at or close to the breakpoints in both chromosome 18 and 11. Full0length cDNAs for normal versions of these genes and any altered forms of these genes resulting from translocation will be isolated and their nucleotide sequence determined. Southern blot, fluorescence in situ hybridization (FISH), and RT-PCR assays for the t(11;18) (q21;q21) will be developed and used to study the distribution and specificity of this translocation in tissues of various lymphomas and hyperplastic lymphoid tissues. Finally, the functions of the genes located near the breakpoints on chromosomes 18 and 11 will be investigated by searching the cDNA sequences for homologies to known genes, determining the normal tissues in which the genes corresponding to these cDNAs are expressed, and testing the oncogenicity of the genes in the form altered as a result of the t(11;18) (q21;21) by inserting appropriate cDNA constructs into transgenic mice. Results of all of these studies will provide insights into the genetic mechanisms underlying the malignant phenotype of the neoplastic lymphocytes composing MALT lymphomas and will likely expand existing knowledge about the normal lymphocytes which represent the cellular precursors of these tumors.