p53 gene mutations inside and outside of exons 5-8: the patterns differ in breast and other cancers.
p53 gene mutations inside and outside of exons 5-8: the patterns differ in breast and other cancers.
复制标题
DOI：
--
复制
发表时间：
1995-02
期刊：
影响因子：
8
通讯作者：
Arndt Hartmann;Hagen Blaszyk;Renee M. McGovern;J. Schroeder;Julie M. Cunningham;E. M. G. D. Vries;John S. Kovach;S. Sommer
中科院分区：
文献类型：
--
作者：
Arndt Hartmann;Hagen Blaszyk;Renee M. McGovern;J. Schroeder;Julie M. Cunningham;E. M. G. D. Vries;John S. Kovach;S. Sommer
大多数关于肿瘤中p53肿瘤抑制基因突变的研究仅检查了外显子5-8。我们的实验室先前在194例原发性乳腺癌中发现了p53基因外显子5-8的64个突变。在此，我们报告了在外显子5-8之外发现的18个额外突变。突变存在于外显子4、9和10以及侧翼剪接点中，但不在启动子区或外显子1、2、3和11中。在外显子5-8之外没有发现错义突变。相反，移码突变占优势，无义和剪接位点突变的数量较少。相比之下，该样本中外显子5-8中的大多数突变是错义变化，并且所有这些突变都位于代表约16亿年进化分歧的11个已知p53序列中相同的氨基酸处。p53基因的这两个区域之间突变模式的差异是由于缺少错义突变和外显子5-8外的框内微缺失。我们的p53突变数据库的综述（De弗里斯et al.，在准备中）显示外显子5-8内部和外部的突变模式在其他类型的癌症中也不同。在乳腺癌和其他癌症中外显子2-4和9-11中缺乏错义突变（甚至在整个p53基因进化中氨基酸相同）表明至少一些错义突变导致恶性转化以外的表型。这些数据也说明了在比较不同人群中p53基因突变模式时检查相同外显子的重要性。
Most studies of mutations in the p53 tumor suppressor gene in tumors have examined only exons 5-8. Our laboratory previously found 64 mutations in exons 5-8 of the p53 gene in 194 primary breast cancers. Herein, we report 18 additional mutations found outside of exons 5-8. Mutations are present in exons 4, 9 and 10, and flanking splice junctions, but not in the promotor region or in exons 1, 2, 3 and 11. No missense mutations are found outside of exons 5-8. Instead, there is a predominance of frameshift mutations with lesser numbers of nonsense and splice site mutations. In contrast, the majority of mutations in exons 5-8 in this sample are missense changes and all of these are at amino acids that are identical in the 11 known p53 sequences that represent about 1.6 billion years of evolutionary divergence. The difference in mutational pattern between these two regions of the p53 gene is due to a lack of missense mutations and inframe microdeletions outside of exons 5-8. A review of our database of p53 mutations (De Vries et al., in preparation) shows that the patterns of mutation inside and outside of exons 5-8 differ in other types of cancers as well. The paucity of missense mutations in exons 2-4 and 9-11 in breast and other cancers (even at amino acids identical throughout p53 gene evolution) suggest that at least some missense mutations result in a phenotype other than malignant transformation. These data also illustrate the importance of examining identical exons when comparing the pattern of p53 gene mutations in different populations.