p53 in head and neck cancer: functional consequences and environmental implications of TP53 mutations.
p53 in head and neck cancer: functional consequences and environmental implications of TP53 mutations.
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DOI：
10.1186/1758-3284-2-36
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发表时间：
2010-12-15
期刊：
影响因子：
--
通讯作者：
Vähäkangas KH
中科院分区：
文献类型：
--
作者：
Peltonen JK;Helppi HM;Pääkkö P;Turpeenniemi-Hujanen T;Vähäkangas KH
尽管TP53在人类肿瘤中的突变已被广泛研究，但p53在头颈癌病因学中的意义仍不完全明确。近年来，人们对p53的突变形式非常感兴趣，p53是TP53等位基因的异常蛋白产物，具有错义突变，经常在癌细胞中积累。我们比较了46例原发性头颈部鳞状细胞癌（HNSCC）中TP53突变的性质，通过PCR-SSCP、测序、免疫组织化学和IARC p53数据库的结构信息进行了分析。测序证实了PCR-SSCP检测到的26个肿瘤中39个突变中的23个肿瘤中36个TP53突变。只有一半（17）被认为影响p53蛋白的功能。其中8个位于L2结构域，3个位于LSH基序，3个位于L3结构域。三个在其他领域。密码子259 （GAC > GAA）是一个非常罕见的突变，在我们的研究中发现了4个样本。有迹象表明，p53异常与吸烟、饮酒和工作经历的综合影响有关。癌症家族史阴性的患者比家族史阳性的患者更容易发生TP53突变（71%对46%）。我们的研究有助于了解头颈癌的累积化学暴露和p53畸变，这是一个文献匮乏的领域。
Although TP53 mutations in human tumours generally have been extensively studied, the significance of p53 in the aetiology of head and neck cancers is still incompletely characterized. In recent years, considerable interest has been focused on mutant forms of p53, the abnormal protein product of TP53 alleles with missense mutation that often accumulate in cancer cells. We compared the nature of TP53 mutations in primary 46 head and neck squamous cell carcinomas (HNSCC) analyzed by PCR-SSCP and sequencing, immunohistochemistry, and using structural information available at IARC p53 database. Sequencing confirmed 36 TP53 mutations in 23 tumours of the 39 mutations in 26 tumours found by PCR-SSCP. Only half (17) putatively affect the function of p53 protein. Of these 8 were in the L2 domain, three affected the LSH motif and three the L3 domain. Three were in other domains. Codon 259 (GAC > GAA) which is a very rare mutation was found in 4 samples in our study. There were indications of p53 aberrations being associated with the combined effect of smoking, alcohol and work history. Patients with a negative family history of cancer had more often TP53 mutations than patients with a positive family history (71% vs. 46%). Our study contributes to the knowledge of cumulative chemical exposure and p53 aberrations in head and neck cancer, an area where literature is scarce.
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影响因子：
56.9
作者：
CHO, YJ;GORINA, S;PAVLETICH, NP
通讯作者：
PAVLETICH, NP
影响因子：
5.6
作者：
Cuff, AL;Martin, ACR
通讯作者：
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8
作者：
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作者：
Chung, Christine H.;Gillison, Maura L.
通讯作者：
Gillison, Maura L.
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影响因子：
7.8
作者：
Gadea, Gilles;de Toledo, Marion;Anguille, Christelle;Roux, Pierre
通讯作者：
Roux, Pierre