Yang Xin-Min, Wu Zhi-Min, Huang Huang, Chu Xiao-Yan, Lou Jun, Xu Li-Xian, Chen Yuan-Ting, Wang Li-Qun, Huang Ou-Ping
College of Medicine, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Key Laboratory of Women's Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China.
Oncol Lett. 2019 Sep;18(3):2771-2776. doi: 10.3892/ol.2019.10612. Epub 2019 Jul 15.
Cervical cancer is one of the leading causes of cancer-associated mortality among females; however, the underlying molecular mechanisms of its carcinogenesis remain largely unclear. Previous comprehensive genomic studies have revealed prevalent estrogen receptor 1 (ESR1) mutations in breast cancer, which are rare in certain other types of cancer. To the best of our knowledge, it is unknown whether ESR1 mutations also exist in cervical cancer. Considering the evidence that cervical cancer shares certain genetic aberrations with breast cancer, and that the progression of both breast and cervical cancers can be affected by estrogen, it is possible that cervical cancer may also harbor ESR1 mutations. In the present study, a total of 260 Chinese cervical cancer samples with distinct subtypes were tested for the presence of ESR1 mutations. A total of three heterozygous missense ESR1 mutations, p.K303R (c.908A>G), p.T311M (c.932C>T) and p.Y537C (c.1610A>G), were identified in 3/207 (1.4%) cervical squamous cell carcinoma samples, which were absent in 27 adenosquamous carcinomas and 26 adenocarcinomas samples. Of the three individuals with an ESR1mutation, 1 patient was also diagnosed with ovarian endometriosis and the other 2 patients were diagnosed with a uterine fibroid. A bioinformatics analysis suggested that these ESR1 mutations may be pathogenic by promoting the development of cervical cancer. Furthermore, a previous comprehensive study confirmed that individuals with cervical squamous cell carcinoma possessed ESR1 mutations. These combined studies indicate that ESR1 mutations may participate in the carcinogenesis of cervical squamous cell carcinoma, albeit at a low frequency. In conclusion, the present study identified three potentially pathogenic ESR1 mutations in Chinese cervical squamous cell carcinoma samples, but not in other subtypes.
宫颈癌是女性癌症相关死亡的主要原因之一；然而，其致癌的潜在分子机制在很大程度上仍不清楚。先前的综合基因组研究揭示了乳腺癌中普遍存在雌激素受体1（ESR1）突变，而在某些其他类型的癌症中则很少见。据我们所知，尚不清楚ESR1突变是否也存在于宫颈癌中。鉴于有证据表明宫颈癌与乳腺癌存在某些共同的基因畸变，并且乳腺癌和宫颈癌的进展都可能受雌激素影响，宫颈癌也可能存在ESR1突变。在本研究中，对总共260例具有不同亚型的中国宫颈癌样本进行了ESR1突变检测。在3/207（1.4%）的宫颈鳞状细胞癌样本中鉴定出总共三个杂合错义ESR1突变，即p.K303R（c.908A>G）、p.T311M（c.932C>T）和p.Y537C（c.1610A>G），而在27例腺鳞癌和26例腺癌样本中未发现这些突变。在这三个具有ESR1突变的个体中，1例患者还被诊断为卵巢子宫内膜异位症，另外2例患者被诊断为子宫肌瘤。生物信息学分析表明，这些ESR1突变可能通过促进宫颈癌的发展而具有致病性。此外，先前的一项综合研究证实，宫颈鳞状细胞癌患者存在ESR1突变。这些综合研究表明，ESR1突变可能参与宫颈鳞状细胞癌的致癌过程，尽管频率较低。总之，本研究在中国宫颈鳞状细胞癌样本中鉴定出三个潜在致病性ESR1突变，但在其他亚型中未发现。
