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

(改编自研究人员的摘要)MALT淋巴瘤构成 新近发现的B细胞非霍奇金淋巴瘤亚型 在粘膜相关淋巴组织(MALT)中，最常见的是 胃肠道。这些肿瘤的不同寻常的特征之一是 异常懒散的整体进程，倾向于停留在本土化 粘膜部位时间长，能力强，可归其他 早期扩散的粘膜部位，反应中的增殖 依赖于或依赖于特定的细菌抗原，并退化或 通过抗生素治疗消除刺激物的细菌源 是 抗原。对这些肿瘤的细胞遗传学研究表明，几乎有一个 四分之一的分析病例含有(11；18)(Q21；Q21)染色体 易位和至少另外四分之一有其他的异常 18号染色体，有时涉及相同的18q21区域。研究 在本应用程序中描述的将分析 T(11；18)(Q21)断裂点 18号染色体和可能的11号染色体DNA。这些碎片将会是 然后用来分离位于或靠近的基因的cDNA片段 18号和11号染色体上的断裂点。 这些基因的正常版本和这些基因的任何改变形式 将分离出易位所致，并对其核苷酸序列进行分析 下定决心。Southern印迹、荧光原位杂交和 将建立t(11；18)(q21；q21)的RT-PCR检测方法，并用于 研究这种易位在非小细胞肺癌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和18号染色体断裂点附近的基因的功能 11将通过搜索cdna序列来研究其同源性 已知的基因，确定基因在哪些正常组织中 与这些cDNA相对应的基因被表达，并检测其致瘤性 由t(11；18)(q21；21)改变的形式的基因 在转基因小鼠中插入适当的cdna构建物。全部结果 这些研究将提供对遗传机制的洞察 肿瘤性淋巴细胞恶性表型的基础 构成MALT淋巴瘤，并可能扩大现有的关于 代表这些细胞前体的正常淋巴细胞 肿瘤。

(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.