Role of BAX mutations in mismatch repair-deficient colorectal carcinogenesis
Role of BAX mutations in mismatch repair-deficient colorectal carcinogenesis
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DOI：
10.1038/sj.onc.1202589
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发表时间：
1999-03-25
期刊：
影响因子：
8
通讯作者：
Wyllie, AH
中科院分区：
文献类型：
--
作者：
Abdel-Rahman, WM;Georgiades, IB;Wyllie, AH
BAX基因突变发生在大约50%的RER+结直肠癌中。为了确定这些突变在肿瘤进展中的作用，我们分析了RER+结直肠癌的多个不同肿瘤部位的BAX突变。对60例结直肠癌进行了BAT-26、L-myc、TGF β RII、D13 S160和D2 S123位点微卫星不稳定性分析。60例肿瘤中有12例（20%）为RER+，分析了12例RER+癌的45个不同肿瘤部位的外显子3 [（G）8]区的BAX突变，12例RER+肿瘤中有6例（50%）显示BAX突变，其中4例显示在所有肿瘤部位均检测到此类突变的同质模式。在另外两种情况下，BAX突变存在于从同一患者采样的一些但不是所有肿瘤部位。相比之下，在9/12例（75%）病例中发现TGF β RII突变，并且在所有采样部位均存在这些突变。2例未发现BAX或TGF β RII突变。这些数据表明，TGF β RII的突变可能发生在肿瘤进展的非常早期阶段，可能发生在创始克隆中。然而，BAX突变显然不是创始人克隆形成所必需的，并且可能在肿瘤进展后期首次发生。
BAX gene mutations occur in approximately 50% of RER+ colorectal cancers. To determine the role of these mutations in tumour progression we analysed multiple different tumour sites from RER+ colorectal cancers for BAX mutations. Sixty colorectal carcinomas were analysed for microsatellite instability at loci BAT-26, L-myc, TGF beta RII, D13S160 and D2S123. Twelve out of 60 tumours (20%) were RER+, Forty-five different tumour sites from the 12 RER+ carcinomas were analysed for BAX mutations at the [(G)8] tract in exon 3, Six out of 12 (50%) RER+ tumours showed BAX mutations, four of which showed a homogenous pattern of such mutations detected in all tumour sites. In the other two cases, BAX mutations were present in some but not all tumour sites sampled from the same patient. In contrast, TGF beta RII mutations were found in 9/12 cases (75%) and in each of these were present in all the sampled sites. Two cases showed neither BAX nor TGF beta RII mutation. These data suggest that mutations in TGF beta RII may occur at a very early stage in tumour progression, perhaps in the founder clone. BAX mutations, however, are clearly not necessary for formation of the founder clone and can occur for the first time later in tumour progression.