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伴有p53 DNA接触突变的口腔鳞状细胞癌的放射抗性

Radioresistance in oral squamous cell carcinoma with p53 DNA contact mutation.

作者信息

Yamazaki Yutaka, Chiba Itsuo, Hirai Atsuko, Notani Ken-ichi, Kashiwazaki Haruhiko, Tei Kanchu, Totsuka Yasunori, Iizuka Tadashi, Kohgo Takao, Fukuda Hiroshi

机构信息

Oral Diagnosis and Oral Medicine, Department of Oral Pathobiological Science, Graduate School of Dental Medicine, Hokkaido University, Kita-13 Nishi-7, Kita-ku, Sapporo 060-8586, Hokkaido, Japan.

出版信息

Am J Clin Oncol. 2003 Oct;26(5):e124-9. doi: 10.1097/01.coc.0000091352.60347.f8.

Abstract

Reliable variables to predict the radiosensitivity of each tumor have not been identified. Recent studies have demonstrated that specific regions of mutations within the core domain of p53 protein correlate with responses to chemotherapy and radiotherapy in some tumor types. In this study, we evaluated the relationship between specific p53 mutations and radiosensitivity in 49 patients with oral squamous cell carcinomas (SCCs) who underwent preoperative radiotherapy. Exons 5 through 8 of the p53 gene were examined by polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. We detected p53 mutations in 27 (55.1%) cases. DNA contact mutations were detected in 11 (40.7%) of these 27 cases in L3 loop, loop-sheet-helix motif, and zinc-binding residues. Tumors containing p53 DNA contact mutations had significantly poorer responses to radiation than the other tumors, although no statistically significant difference between tumors with and without p53 mutations was found. These data indicate that DNA contact mutation of p53 could be a useful marker to predict the radioresistance of oral SCCs.

摘要

尚未确定预测每种肿瘤放射敏感性的可靠变量。最近的研究表明,p53蛋白核心结构域内特定的突变区域与某些肿瘤类型对化疗和放疗的反应相关。在本研究中,我们评估了49例接受术前放疗的口腔鳞状细胞癌(SCC)患者中特定p53突变与放射敏感性之间的关系。通过聚合酶链反应-单链构象多态性和直接测序检测p53基因的第5至8外显子。我们在27例(55.1%)病例中检测到p53突变。在这27例病例中的11例(40.7%)中,在L3环、环-片-螺旋基序和锌结合残基中检测到DNA接触突变。尽管在有和没有p53突变的肿瘤之间未发现统计学上的显著差异,但含有p53 DNA接触突变的肿瘤对放疗的反应明显比其他肿瘤差。这些数据表明,p53的DNA接触突变可能是预测口腔SCC放射抗性的有用标志物。

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