Analysis of Tp53 codon 72 polymorphisms, Tp53 mutations, and HPV infection in cutaneous squamous cell carcinomas.
Analysis of Tp53 codon 72 polymorphisms, Tp53 mutations, and HPV infection in cutaneous squamous cell carcinomas.
复制标题
DOI：
10.1371/journal.pone.0034422
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kiviat NB
中科院分区：
文献类型：
--
作者：
Loeb KR;Asgari MM;Hawes SE;Feng Q;Stern JE;Jiang M;Argenyi ZB;de Villiers EM;Kiviat NB
非黑色素瘤皮肤癌是最常见的人类恶性肿瘤之一，占美国肿瘤的2-3%，并且代表了显著的健康负担。流行病学研究表明，由紫外线照射引发的Tp 53突变和人乳头瘤病毒（HPV）感染是非黑色素瘤皮肤癌的重要原因。然而，在皮肤癌中，TP 53和皮肤HPV感染之间的关系尚不清楚。在这项研究中，我们评估了HPV感染和Tp 53基因多态性和突变与鳞状细胞癌的关系。我们研究了55例经组织学证实的皮肤鳞状细胞癌和41例对照的HPV感染和TP 53基因型（突变和多态性）的存在。我们发现，与病灶周围或对照组相比，鳞状细胞癌样本中的Tp 53突变数量增加。结果表明，Tp 53 - 72 R纯合子多态性在鳞状细胞癌中的频率明显增高，而Tp 53 - 72 P等位基因（Tp 53 - 72 R/P和Tp 53 - 72 P/P）在正常对照组中的频率明显增高。与没有HPV感染的癌样本相比，HPV阳性的癌样本显示Tp 53突变频率降低。此外，具有Tp 53 - 72 P等位基因的癌样品显示与Tp 53 - 72 R纯合的癌样品相比Tp 53突变的发生率增加。这些研究表明，有两个独立的途径（HPV感染和TP 53突变）导致皮肤鳞状细胞癌分层的TP 53密码子-72多态性。Tp 53 - 72 P等位基因的存在对皮肤鳞状细胞癌具有保护作用，并且具有Tp 53 - 72 P的癌标本更可能具有Tp 53突变。相反，Tp 53 - 72 R是皮肤鳞状细胞癌的重要危险因素，并且通常与HPV感染而不是Tp 53突变相关。Tp 53 - 72 R/P的杂合性对鳞状细胞癌具有保护作用，可能反映了HPV感染和Tp 53突变的要求。
Non-melanoma skin cancers are one of the most common human malignancies accounting for 2–3% of tumors in the US and represent a significant health burden. Epidemiology studies have implicated Tp53 mutations triggered by UV exposure, and human papilloma virus (HPV) infection to be significant causes of non-melanoma skin cancer. However, the relationship between Tp53 and cutaneous HPV infection is not well understood in skin cancers. In this study we assessed the association of HPV infection and Tp53 polymorphisms and mutations in lesional specimens with squamous cell carcinomas. We studied 55 cases of histologically confirmed cutaneous squamous cell carcinoma and 41 controls for the presence of HPV infection and Tp53 genotype (mutations and polymorphism). We found an increased number of Tp53 mutations in the squamous cell carcinoma samples compared with perilesional or control samples. There was increased frequency of homozygous Tp53-72R polymorphism in cases with squamous cell carcinomas, while the Tp53-72P allele (Tp53-72R/P and Tp53-72P/P) was more frequent in normal control samples. Carcinoma samples positive for HPV showed a decreased frequency of Tp53 mutations compared to those without HPV infection. In addition, carcinoma samples with a Tp53-72P allele showed an increased incidence of Tp53 mutations in comparison carcinomas samples homozygous for Tp53-72R. These studies suggest there are two separate pathways (HPV infection and Tp53 mutation) leading to cutaneous squamous cell carcinomas stratified by the Tp53 codon-72 polymorphism. The presence of a Tp53-72P allele is protective against cutaneous squamous cell carcinoma, and carcinoma specimens with Tp53-72P are more likely to have Tp53 mutations. In contrast Tp53-72R is a significant risk factor for cutaneous squamous cell carcinoma and is frequently associated with HPV infection instead of Tp53 mutations. Heterozygosity for Tp53-72R/P is protective against squamous cell carcinomas, possibly reflecting a requirement for both HPV infection and Tp53 mutations.
登录
查看更多内容
影响因子：
30.8
作者：
Dumont, P;Leu, JIJ;Murphy, M
通讯作者：
Murphy, M
影响因子：
6.4
作者：
Fei, Jian-Wei;de Villiers, Ethel-Michele
通讯作者：
de Villiers, Ethel-Michele
影响因子：
4.3
作者：
Fei, JW;Wei, QX;de Villiers, EM
通讯作者：
de Villiers, EM
影响因子：
5
作者：
Caceres, Dante D.;Quinones, Luis A.;Irarrazabal, Carlos E.
通讯作者：
Irarrazabal, Carlos E.
影响因子：
30.8
作者：
DITTMER, D;PATI, S;LEVINE, AJ
通讯作者：
LEVINE, AJ