Role of p53 gene mutations in the multi-step car cinogenesis of head and neck squamous cell car cinomas

为探讨头颈部鳞状细胞癌患者吸烟史与p53基因突变频率的关系，采用聚合酶链式反应-单链构象多态性分析及DNA直接测序的方法，对18例头颈部鳞癌DNA标本进行了p53基因突变检测。在18例肿瘤标本中发现5个p53基因突变(28%)。其中1例外显子5有微小缺失，4例外显子5有点突变，其中3例为密码子175位的G向A转换，1例为密码子143位的T向C转换。在5例P53基因突变患者中，4例有重度吸烟史，而13例无P53基因突变的患者中只有3例有吸烟史。这种p53基因突变模式不同于另外两种与烟草相关的肿瘤-食道癌和肺癌，其中G：C到T：A易位是最常见的替换。研究表明，有大量吸烟史的头颈癌患者可能普遍存在P53基因功能的改变，但与肺癌和食道癌不同的诱变剂或突变过程可能参与了头颈癌P53基因突变的产生。

Toinvestigate the correlation between patients' smoking history and the frequency of p53 gene mutations in squamous cell car cinomas of the head and neck, 18 DNA samples from head and neck car cinoma specimens were investigated for the presence of p53 gene mutations by polymerase chain reaction (PCR)-single strand confor mation polymor phisms (SSCP) analysis followed by direct DNA sequencing. Five mutations of the p53 gene were identified (28%) in 18 tumor samples. One sample showed a small deletion in exon 5 and four samples showed a point mutation in exon 5, three of these mutations were G to Atransitions at codon 175 and one was a T to C transition at codon 143. Of 5 patients with p53 gene mutations, 4 had a history of heavy smoking, whereas only 3 of 13 patients without p53 gene mutations had such a history. This p53 gene mutation pattern differs from those reported in esophageal and lung cancers, two other tobacco-associated neoplasms, in which G : C to T : A transversions are the most frequent substitution.Findings suggest that alteration in p53 gene function may be common in patients with head and neck cancers with a history of heavy smoking, however, mutagens or mutagenic processes that differ from those in lung and esophageal cancers may beinvolved in the generation of p53 gene mutations in head and neck cancers.