Du M Q, Xu C F, Diss T C, Peng H Z, Wotherspoon A C, Isaacson P G, Pan L X
Department of Histopathology, University College London Medical School, UK.
Blood. 1996 Dec 15;88(12):4445-51.
Despite increasing identification of concurrent gastric and intestinal lymphomas of mucosa-associated lymphoid tissue (MALT), the clonal relationship between the two tumors and their sequential development are poorly understood. It is also unknown whether the development of these concurrent tumors is closely associated with direct antigen stimulation, which is thought to play an important role in the clonal expansion of low-grade MALT lymphomas. To investigate these, we have studied six cases of concurrent gastric and intestinal MALT lymphomas by polymerase chain reaction (PCR) amplification, cloning, and sequencing of the rearranged Ig gene, a strategy that has been widely used for analysis of clonality and antigen-driven properties of B-cell malignancies. In each case, an identical or nearly identical complementarity determining region (CDR) 3 sequence was observed between the dominant clones of concurrent gastric and intestinal MALT lymphomas. In four of six cases examined, sufficient Ig variable region sequence information was obtained to permit analysis of somatic mutations. The mutation patterns in one case suggest that the intestinal lesion is secondary to the gastric tumor, and the mutation patterns in two cases indicate that the gastric and intestinal lesions are derived from different tumour subclones, which emerge after expansion of a common early tumor clone. Furthermore, three of four cases showed ongoing Ig mutations among different PCR clones at each site. These results show that concurrent gastric and intestinal MALT lymphomas are derived from the same clone and suggest that the intestinal lesions result from dissemination of gastric tumours. Antigen stimulation may play a role in tumor evolution, particularly at an early stage.
尽管黏膜相关淋巴组织（MALT）同时发生的胃和肠道淋巴瘤的识别率不断提高，但对这两种肿瘤之间的克隆关系及其相继发展情况仍知之甚少。这些同时发生的肿瘤的发展是否与直接抗原刺激密切相关也不清楚，而直接抗原刺激被认为在低度MALT淋巴瘤的克隆扩增中起重要作用。为了研究这些问题，我们通过聚合酶链反应（PCR）扩增、克隆以及对重排的Ig基因进行测序，对6例同时发生的胃和肠道MALT淋巴瘤进行了研究，这一策略已广泛用于分析B细胞恶性肿瘤的克隆性和抗原驱动特性。在每例中，同时发生的胃和肠道MALT淋巴瘤的优势克隆之间观察到相同或几乎相同的互补决定区（CDR）3序列。在检测的6例中的4例中，获得了足够的Ig可变区序列信息以进行体细胞突变分析。1例中的突变模式表明肠道病变继发于胃肿瘤，2例中的突变模式表明胃和肠道病变源自不同的肿瘤亚克隆，这些亚克隆在一个共同的早期肿瘤克隆扩增后出现。此外，4例中的3例在每个部位的不同PCR克隆中显示出持续的Ig突变。这些结果表明，同时发生的胃和肠道MALT淋巴瘤源自同一克隆，并提示肠道病变是胃肿瘤播散的结果。抗原刺激可能在肿瘤演变中起作用，尤其是在早期阶段。
