Peng H, Aiello A, Packham G, Isaacson P G, Pan L
Department of Histopathology, UCL Medical School, London, U.K.
J Pathol. 1998 Dec;186(4):378-82. doi: 10.1002/(SICI)1096-9896(199812)186:4<378::AID-PATH203>3.0.CO;2-5.
Mutation of the bax gene has been reported previously in lymphoid cell lines. In vitro experiments have shown that alterations in promoter and coding sequences of the gene abolish its apoptosis initiation function, which is considered crucial for tumour development. To assess bax gene mutations in lymphomagenesis, polymerase chain reaction-based single strand conformation polymorphism analysis (PCR-SSCP) and direct sequencing were used to detect altered sequences in the promoter region and all the six exons and their flanking sequences of the gene. Nodal and extranodal B-cell lymphomas (n = 112) including follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, splenic marginal zone B-cell lymphoma and low- and high-grade mucosa-associated lymphoid tissue (MALT) lymphomas were studied. Sequence alterations were found in 11 cases. Nine also showed the same altered sequences in corresponding non-tumour control tissue samples, indicating polymorphism. In the remaining two cases, sequence alterations (in exons 3 and 6) which altered the bax open reading frame were observed only in tumour tissues, indicating tumour-specific point mutation. These results suggest that inhibition of apoptosis through bax gene mutations is unlikely to be a common event in B-cell lymphoma, at least in the major types of nodal and extranodal B-cell lymphomas.
先前已有报道称bax基因在淋巴样细胞系中发生了突变。体外实验表明，该基因启动子和编码序列的改变会使其凋亡起始功能丧失，而这一功能被认为对肿瘤发展至关重要。为了评估bax基因突变在淋巴瘤发生中的作用，采用基于聚合酶链反应的单链构象多态性分析（PCR-SSCP）和直接测序法来检测该基因启动子区域以及所有六个外显子及其侧翼序列中的序列改变。研究了包括滤泡性淋巴瘤、套细胞淋巴瘤、弥漫性大B细胞淋巴瘤、脾边缘区B细胞淋巴瘤以及低级别和高级别黏膜相关淋巴组织（MALT）淋巴瘤在内的淋巴结和结外B细胞淋巴瘤（n = 112）。在11例病例中发现了序列改变。其中9例在相应的非肿瘤对照组织样本中也显示出相同的改变序列，表明为多态性。在其余2例病例中，仅在肿瘤组织中观察到改变了bax开放阅读框的序列改变（外显子3和6），表明为肿瘤特异性点突变。这些结果表明，通过bax基因突变抑制凋亡在B细胞淋巴瘤中不太可能是常见事件，至少在主要类型的淋巴结和结外B细胞淋巴瘤中如此。
