Estrogen receptor 1 mutations in 260 cervical cancer samples from Chinese patients

Abstract

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.

miR‑130a‑3p promotes cell proliferation and invasion by targeting estrogen receptor α and androgen receptor in cervical cancer

“…Estrogen and its analogs can activate estrogen-responsive genes by binding to estrogen receptor α (ERα) ( 7 ). Previous genomic studies have identified frequent mutations of the ERα gene (ESR1) in CC ( 8 , 9 ). Additionally, it has been demonstrated that viral-codified E6 and E7 proteins could directly interact with androgen receptor (AR) ( 10 ).…”

Anticancer Melatplatin Prodrugs: High Effect and Low Toxicity, MT1-ER-Target and Immune Response In Vivo

“…4 According to the reports, there were approximately 75% of BC patients with ER highly expressed. 5 Besides, ER was also found overexpressed in many different kinds of tumors, such as estrogen-dependent ovarian cancer, 6 endometrial cancer, 7 cervical cancer, 8 estrogen-independent liver cancer, 9 gastric cancer, 10 lung cancer, 11 colorectal cancer, 12 etc. ER is therefore considered to be a key indicator in clinical treatment and prognosis.…”

Detection of ESR1 Mutations in Primary Tumors and Plasma Cell-Free DNA in High-Grade Serous Ovarian Carcinoma Patients

“…To date, the detection of ESR1 mutations has been reported in cervical squamous cell carcinoma [ 26 ] and in a patient with endometrial cancer treated with an aromatase inhibitor [ 27 ]. It has also been reported that the presence of ESR1 mutations is associated with worse outcomes in endometrial cancer [ 28 ].…”

“…ESR1 mutations have emerged as a key mechanism of resistance to endocrine therapy in patients with ER-positive metastatic breast cancer [ 24 ] and their detection is now considered to be highly promising as a prognostic and predictive biomarker in this type of cancer [ 24 , 25 ]. To date, only a few studies have investigated the presence of ESR1 mutations in endometrial and cervical cancer [ 26 , 27 , 28 , 29 , 30 ]. According to the cBioPortal cancer genomics database, ESR1 mutations have been detected in 4–6% of uterine corpus endometrial carcinoma samples [ 31 ].…”