p53 mutations in Hodgkin's disease.
p53 mutations in Hodgkin's disease.
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发表时间：
1996-10
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通讯作者：
Wen-gun Chen;Yuan-yuan Chen;O. Kamel;C. Koo;L. Weiss
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作者：
Wen-gun Chen;Yuan-yuan Chen;O. Kamel;C. Koo;L. Weiss
虽然许多研究表明，增加了p53蛋白的表达在里德-斯滕伯格细胞的霍奇金病，很少有数据存在，以是否突变的p53基因是一个常见的发生在这种肿瘤。采用显微切割技术结合PCR、单链构象分析和DNA测序，我们研究了23例霍奇金病p53基因外显子5至8内的突变。我们在六个病例中发现了七个突变;六个是错义突变。一个相同的错义突变被发现在三个案件（密码子243，蛋氨酸异亮氨酸），另一个相同的错义突变被发现在另外两个案件（密码子204，谷氨酸赖氨酸）。突变的验证可以通过对重新提取的DNA中PCR扩增的p53外显子产物进行直接Southern印迹来完成，也可以通过将重新提取的DNA中克隆的PCR扩增的p53外显子产物与突变体特异性寡核苷酸杂交来完成。p53突变的存在和p53蛋白表达水平之间没有良好的相关性，发现在所有情况下都过表达，MDM 2蛋白表达水平或K-67抗体测定的增殖率。p53基因突变的病例中没有一个在Reed-Sternberg细胞内发现EB病毒的证据，而其他17例病例中有7例（p < 0.06）。提示p53基因突变可能是霍奇金病发病机制中的一个重要环节，且可能与EB病毒无关。
Although numerous studies have demonstrated increased expression of p53 protein in the Reed-Sternberg cells of Hodgkin's disease, little data exist as to whether mutations of the p53 gene is a common occurrence in this neoplasm. Using a microdissection technique coupled with PCR, single-strand conformation analysis, and DNA sequencing, we studied 23 cases of Hodgkin's disease for mutations within exons 5 to 8 of the p53 gene. We found seven mutations within six cases; six were missense mutations. An identical missense mutation was found in three cases (codon 243, methionine to isoleucine), and another identical missense mutation was found in an additional two cases (codon 204, glutamic acid to lysine). Verification of the mutations was accomplished either by direct Southern blotting of PCR-amplified p53 exon products from re-extracted DNA or by hybridization of cloned PCR-amplified p53 exon products from re-extracted DNA with a mutant-specific oligonucleotide. There was no good correlation between the presence of p53 mutations and the level of p53 protein expression, which was found to be overexpressed in all cases, the level of MDM2 protein expression, or the proliferation rate as determined by K-67 antibody. None of the cases with p53 mutation had evidence of Epstein-Barr virus within the Reed-Sternberg cells, as compared with 7 of 17 of the other cases (p < 0.06). These results suggest that p53 mutation may represent an important mechanism in the pathogenesis of Hodgkin's disease, and this mechanism may be independent of Epstein-Barr virus.