儿童肾母细胞瘤相关基因CTNNB1和WT1突变的初步研究

Studies on CTNNB1 and WT1 mutations in pediatric patients with Wilm＇s tumor

目的观察CTNNB1和WT1基因在我国肾母细胞瘤患儿中的突变特点，探索基因突变与患儿临床表现之间的关系。方法随机选取我院2007年1月至2011年1月收治的肾母细胞瘤患儿50例。收集这些病例的临床资料，并对肿瘤组织和瘤旁组织的CTNNB1基因外显子3、7、8、9和WT1基因外显子1～10进行突变检测。结果CTNNB1突变15例（30％），8例突变涉及第45位点的丝氨酸编码子（TCT），其中2例完全丢失，6例错义突变。剩余7例为错义突变。wTl突变9例（18％）。移码突变4例，无义突变3例，2例碱基插入突变发生在内含子1区域。CTNNB1和WT1突变与患儿临床表现未见显著相关（P〉0．05）。CTNNBl突变与WT1突变明显相关（P〈0．002）。结论CTNNB1和WT1基因突变确实存在于我国儿童肾母细胞瘤患者中。CTNNB1突变患儿存在WT1突变概率明显高于无CTNNB1突变患儿。然而尚未发现CTNNBl和WT1突变与患儿临床表现密切相关。

Objective To investigate the CTNNB1 and WT1 mutations in Chinese pediatric pa- tients with Wilm＇s tumor and to explore the correlations between mutations of these two genes and the patients＇ clinical characteristics. Methods Fifty cases with Wiln-rs tumors who were treated in our hos- pital from Jan of 2007 to Jan of 2011 were included in this study. The clinical variables were reviewed. DNA was collected from tissue of tumor and normal kidney beside tumor. Exon 3,7-9 of CTNNB1 and exon 1-10 of WTI were sequenced. Results There were 15 （30%） cases with somatic mutations of CTNNB1. Eight mutations at codon 45 included 2 TCT deletions and 6 mis-sense mutations. The rest were 7 different mis-sense mutations. There were 9 patients （18%） with WT1 mutations including 4 frame shift and 3 nonsense mutations. The other 2 same insert mutations existed at intron 1 region. No significant correlation was found between mutations of CTNNB1/WT1 and clinical characteristics （P 〈0. 05）. However there was significant correlation between CTNNB1 and WTI mutations （P = 0. 002）. Conclusions Mutations of CTNNB1 and WT1 do exist in Chinese pediatric patients with Wilm＇s tumor. Tumors with CTNNBI mutations are more likely to have WT1 mutations. Nevertheless there is no significant correlation between clinical variahles and gene mutations.