Open Access

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

  • Authors:
    • Xin‑Min Yang
    • Zhi‑Min Wu
    • Huang Huang
    • Xiao‑Yan Chu
    • Jun Lou
    • Li‑Xian Xu
    • Yuan‑Ting Chen
    • Li‑Qun Wang
    • Ou‑Ping Huang
  • View Affiliations

  • Published online on: July 15, 2019     https://doi.org/10.3892/ol.2019.10612
  • Pages: 2771-2776
  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

Introduction

Cervical cancer is one of the leading causes of cancer-associated mortality among females worldwide (1,2). Despite the existence of a safe vaccine against human papillomavirus (HPV) and an early screening test for cervical cancer, the frequency of females undergoing the test is not sufficient (3,4). Furthermore, an insufficient number of HPV vaccines are available in countries that exhibit a high prevalence rate of cervical cancer and the worldwide incidence rate of cervical cancer has not significantly decreased (5,6). Therefore, there is a requirement to explore the underlying molecular mechanisms of cervical cancer.

Estrogen receptor 1 (ESR1) is a transcription factor that can be activated by estrogen and other growth factors in a ligand-dependent manner; activated ESR1 dimerizes and regulates the transcription of numerous target genes (7,8). Previous comprehensive genomic studies have revealed frequent ESR1 mutations in metastatic types of breast cancer (9,10). Subsequent studies also confirmed these observations (1113) and demonstrated that ESR1-mutated samples often exhibit increased resistance to aromatase inhibitors (14). In addition, ESR1 mutations have been identified in endometrial (15) and colorectal cancer (16) at low frequencies. However, to the best of our knowledge, it remains unknown whether ESR1 mutations exist in other types of cancer, including cervical cancer.

Cervical cancer shares certain genetic aberrations with breast cancer, including frequent mutations in the PIK3CA, TP53, PTEN and ARID1A genes (1721), and the development of cervical and breast cancer can be affected by estrogen action (2225). These similarities suggest that cervical cancer may also harbor ESR1 mutations. To test this hypothesis, a total of 260 samples from Chinese patients with distinct subtypes of cervical cancer were investigated for the presence of ESR1 mutations. A total of three heterozygous missense ESR1 mutations were identified in 207 samples of cervical squamous cell carcinoma (3/207, 1.4%), whereas no mutations were detected in the 27 adenosquamous carcinoma or 26 adenocarcinomas samples. The identified ESR1 mutations could have predictive values and may provide insights into the diagnosis and molecular therapy of cervical cancer.

Patients and methods

Formalin-fixed, paraffin-embedded (FFPE) samples

The sample cohort has been previously described (26). Briefly, a total of 260 FFPE cancerous and paired adjacent non-cancerous tissue sections (10 µm), including squamous cell carcinoma (n=207), adenosquamous carcinoma (n=27) and adenocarcinoma (n=26) tissues, were fixed in 10% neutral buffered formalin for 36 h at room temperature, and collected from the archives of the Department of Pathology at the Jiangxi Provincial Maternal and Child Health Hospital (Nanchang, China) between July 2008 and August 2013. The median age of patients was 43 years old (range, 22–74 years). The present study was approved by the Institutional Review Board of Jiangxi Provincial Maternal and Child Health Hospital (Nanchang, China), and performed according to the Declaration of Helsinki. All patients provided written informed consent prior to the study.

Mutation analysis

Genomic DNA was isolated using QIAamp DNA FFPE Tissue kit (Qiagen GmbH, Hilden, Germany). The entire coding exons and the corresponding intron/exon boundaries of the ESR1 gene were amplified with a set of primer pairs (Table I). The polymerase chain reaction (PCR) amplification was performed in a 50 µl reaction volume containing 0.2 µM deoxyribonucleotide triphosphate, 5 µl 10X PCR buffer, 0.5 U rTaq DNA Polymerase (Takara Biotechnology Co., Ltd., Dalian, China) and 200 ng genomic DNA. PCR amplifications were performed in a Bio-Rad iCycler thermal cycler (Bio-Rad Laboratories, Inc., Hercules, CA, USA) with the following conditions: 94°C for 3 min, 35 cycles of 94°C for 30 sec, 50–58°C for 30 sec and 72°C for 30 sec, and a final extension step at 72°C for 10 min. The amplicons were sequenced bidirectionally on an ABI 3730 Genetic Analyzer (Thermo Fisher Scientific, Inc., Waltham, MA, USA) and the sequencing data was aligned against the corresponding genomic sequence (ESR1, NM_000125) in the National Center for Biotechnology Information (NCBI) database (www.ncbi.nlm.nih.gov). The identified somatic mutations were confirmed by sequencing the paired, adjacent non-cancerous tissues.

Table I.

Primer sequences used for polymerase chain reaction amplification of the estrogen receptor 1 gene.

Table I.

Primer sequences used for polymerase chain reaction amplification of the estrogen receptor 1 gene.

ExonForward primer (5′-3′)Reverse primer (5′-3′)Annealing temperature (°C)Amplicon length (bp)
1–1 GAGCCTTCTGCCCTGCGG GGTCTGACCGTAGACCTG53270
1–2 CCGCGGCCGCCGCCAACG GGCGCGGGCGCGGGTAC50279
2 TAATGTTAATGGATTTAC TTCAACACACTATTACCT56242
3 TAGATTCTGACTGGCTAA CTGGGAGAGATGTACCTA52197
4–1 TGTATAAAAGTTTACACG GCACTGACCATCTGGTCG52253
4–2 TGGCCTTGTCCCTGACG GTTCTTGAAAAGCTATTG58228
5 TCATTTGAGTCAGCAGG GCTACAGCCAGGTCACTTA58197
6 TCATGTCTTGTGGAAGA ATCTTGTGTTATCAACTC53226
7 TCTCACTCTCTCTCTGC GTAGGAAGCCCACAGAT55233
8 TGTCTTCCCACCTACAG GGAGCTCTCAGACCGTGG57259
In silico analysis of the ESR1 mutations

Two online prediction programs, MutationTaster (http://www.mutationtaster.org) (27) and Polymorphism Phenotyping v2 (PolyPhen-2; http://genetics.bwh.harvard.edu/pph2) (28), were used to predict the associations between the identified ESR1 mutations and disease occurrence. These programs assessed the identified ESR1 mutations as either ‘benign’ or ‘pathogenic’, according to the automatically predicted score.

Evolutionary conservation analysis

The evolutionary conservation of the mutated amino acids of ESR1 was analyzed in a total of 18 vertebrate species retrieved from the NCBI database, including Homo sapiens (NP_000116), Pan troglodytes (XP_009450519), Mus musculus (NP_001289460), Rattus norvegicus (NP_036821), Ovis aries (NP_000116), Bos taurus (NP_001001443), Gallus gallus (NP_990514), Sus scrofa (NP_999385), Canis lupus familiaris (NP_001273887), Equus caballus (NP_001075241), Tupaia chinensis (NP_001304001), Mustela putorius furo (XP_004753629), Oryctolagus cuniculus (XP_008261925), Pongo abelii (XP_002817538), Coturnix japonica (NP_001310118), Alligator sinensis (XP_014375965), Ceratotherium simum simum (NP_001266182) and Xenopus tropicalis (NP_988866). The Molecular Evolutionary Genetics Analysis 4.0 software (29) was used for multiple sequence alignment.

Protein structure modeling

DeepView Swiss-PdbViewer 4.0 software (30) was used to predict the potential protein structural changes for the identified ESR1 mutations. An available 3D protein structure of human ESR1 (protein data bank code, 2OCF) (31) was retrieved from the SWISS-MODEL repository in the ExPasy web interface (http://www.expasy.org).

Results

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 from 207 cervical squamous cell carcinoma samples (3/207, 1.4%), while no mutations were detected in the adenosquamous carcinoma and adenocarcinoma samples. The mutations were absent in the paired non-cancerous tissues and were therefore considered to be somatic (Fig. 1). The K303R and T311M mutations are located in the ‘hingeregion’ and the Y537C mutation is located in the ‘ligand-binding domain’ (9,10). Of the three individuals with ESR1 mutations, two were further diagnosed with uterine fibroid and one with ovarian endometriosis.

In silico analysis of the ESR1 mutations

Two publicly available bioinformatics programs, MutationTaster and PolyPhen-2, were used to predict the potential functional significance of the ESR1 mutations. The predictions by MutationTaster for the three ESR1 mutations (p.K303R, p.T311M and p.Y537C) were ‘disease causing’ and ‘protein features (might be) affected’, while PolyPhen-2 predicted these mutations to be ‘probably damaging’ (p.T311M and p.Y537C) or ‘possibly damaging’ (p.K303R), with a prediction score of >0.90. Furthermore, the Y537C (c.1610A>G) and K303R (c.908A>G) mutations were not identified in the 1,000Genomes (https://www.ncbi.nlm.nih.gov/variation/tools/1000genomes/) (32) or the Exome Aggregation Consortium (EXAC; http://exac.broadinstitute.org/) (33) databases, while the p.T311M (c.932C>T) mutation was identified in the general population with an extremely low frequency (1/121,362) in the EXAC database.

Evolutionary conservation analysis and protein structural modeling

The results of evolutionary conservation analysis demonstrated that the three ESR1 mutations were associated with highly conserved amino acid changes among 18 vertebrate species, ranging from Homo sapiens to Xenopus tropicalis (Fig. 2). The protein structural prediction results suggested that the three ESR1 mutations may induce the structural changes in the side chain of ESR1 protein (Fig. 3); results that were consistent with the prediction results by MutationTaster.

Discussion

Previous studies have identified prevalent ESR1 mutations in breast cancer (9,10); however, it remains largely unknown whether ESR1 mutations exist in other types of cancer, including cervical cancer.

In the present study, a total of 260 samples from Chinese patients with distinct subtypes of cervical cancer were tested for the presence of ESR1 mutations. In total, three missense somatic mutations in ESR1, p.K303R (c.908A>G), p.T311M (c.932C>T) and p.Y537C (c.1610A>G), were identified from 207 squamous cell carcinomas (3/207, 1.4%), which were not present in other cervical cancer subtypes. Evolutionary conservation analysis demonstrated that the three ESR1 mutations were associated with highly conserved amino acid, which may describe the potential to cause protein structural changes. In silico analysis suggested that these mutations may be pathogenic. Furthermore, the three ESR1 mutations have previously been identified in other types of cancer. The p.K303R (c.908A>G) mutation has been observed in 206/6,556 samples of breast cancer (2437). The p.T311M (c.932C>T) mutation has been identified in 2/2,218 colorectal cancer samples (38) and 1/2,105 liver cancer samples (38). In addition, the p.Y537C (c.1610A>G) mutation has been detected in 10/6,556 breast cancer samples (11,3941). Similarly, a previous comprehensive study identified ESR1 somatic mutations p.K206R (c.617A>G) and p.L372L (c.1116C>G) in 2/306 (0.7%) cervical squamous cell carcinoma samples (http://cancer.sanger.ac.uk/cosmic). However, a previous genomic analysis of cervical cancer failed to detect any ESR1 mutations in 79 squamous cell carcinoma samples (17). Considering the low frequency of ESR1 mutation in cervical squamous cell carcinoma, it is suggested that the small sample size analyzed in this previous study may have caused the inconsistency in the results (17). In combination, both previous studies and the present study suggest that ESR1 mutations may participate in the carcinogenesis of cervical cancer, albeit at a low frequency.

A number of previous functional assays for the identified ESR1 mutations, including p.K303R (42) and p.Y537C (9,43), demonstrated that these mutations are associated with acquired endocrine resistance in hormonal therapy in breast cancer (7,8,40,41). Therefore, it is proposed that the ESR1 mutations identified in cervical cancer in the present study may further cause acquired endocrine resistance to hormonal therapy in breast cancer.

Antihormonal agents have recently been used to improve effects of chemo- and radiotherapy in cervical cancer (44). However, due to the potential acquired endocrine resistance in cervical cancer samples with ESR1 mutations, antihormonal agents should be used with caution during chemo-and radiotherapy.

The three ESR1 mutations were not detected in the 27 adenosquamous carcinoma or the 26 adenocarcinoma samples of the present study, which is consistent with a prior genomic analysis of cervical cancer with distinct subtypes, in which no ESR1 mutations were detected in either 24 adenocarcinoma or 7 adenosquamous carcinoma samples (17). In summary, these results suggest that the ESR1 mutations may not be positively involved in the pathogenesis of cervical adenocarcinoma and adenosquamous carcinoma. However, the absence of ESR1 mutations in patients with adenosquamous carcinoma and adenocarcinoma may be due to the small sample sizes analyzed in the present study.

In conclusion, the current study identified three potentially pathogenic ESR1 mutations in cervical squamous cell carcinoma samples from Chinese patients, which were not observed in other subtypes. These results, together with numerous previous studies, suggested that ESR1 mutations may be involved in the carcinogenesis of squamous cell carcinoma, but not in other subtypes of cervical cancer.

Acknowledgements

Not applicable.

Funding

The present study was supported by grants from the Natural Science Foundation of China (grant no. 81160079) and the Natural Science Foundation of Jiangxi Province (grant nos. 20143ACG70016 and 20161ACB21021).

Availability of data and materials

All the data generated or analyzed during the present study are available from the corresponding author on reasonable request.

Authors' contributions

XMY, HH, LXX and YTC performed the experiments. ZMW and LQW analyzed the data. XYC and JL collected samples and clinical data. XMY prepared the manuscript. OPH designed the study and revised the manuscript.

Ethics approval and consent to participate

The experimental protocol was established according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of Nanchang University. Written informed consent was obtained from all participants or their guardian.

Patients consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

References

1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Jemal A, Simard EP, Dorell C, Noone AM, Markowitz LE, Kohler B, Eheman C, Saraiya M, Bandi P, Saslow D, et al: Annual report to the nation on the status of cancer, 1975–2009, featuring the burden and trends in human papillomavirus (HPV)-associated cancers and HPV vaccination coverage levels. J Natl Cancer Inst. 105:175–201. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Pedersen K, Burger EA, Nygård M, Kristiansen IS and Kim JJ: Adapting cervical cancer screening for women vaccinated against human papillomavirus infections: The value of stratifying guidelines. Eur J Cancer. 91:68–75. 2018. View Article : Google Scholar : PubMed/NCBI

4 

Philp L, Jembere N, Wang L, Gao J, Maguire B and Kupets R: Pap tests in the diagnosis of cervical cancer: Help or hinder? Gynecol Oncol. 150:61–66. 2018. View Article : Google Scholar : PubMed/NCBI

5 

Bogani G, Leone Roberti Maggiore U, Signorelli M, Martinelli F, Ditto A, Sabatucci I, Mosca L, Lorusso D and Raspagliesi F: The role of human papillomavirus vaccines in cervical cancer: Prevention and treatment. Crit Rev Oncol Hematol. 122:92–97. 2018. View Article : Google Scholar : PubMed/NCBI

6 

Lytwyn A, Elit L and Sellors JW: Human papillomavirus DNA versus papanicolaou screening tests for cervical cancer. N Engl J Med. 358:6412008. View Article : Google Scholar : PubMed/NCBI

7 

Yaşar P, Ayaz G, User SD, Güpür G and Muyan M: Molecular mechanism of estrogen-estrogen receptor signaling. Reprod Med Biol. 16:4–20. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Bado I, Gugala Z, Fuqua SAW and Zhang XH: Estrogen receptors in breast and bone: From virtue of remodeling to vileness of metastasis. Oncogene. 36:4527–4537. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Robinson DR, Wu YM, Vats P, Su F, Lonigro RJ, Cao X, Kalyana-Sundaram S, Wang R, Ning Y, Hodges L, et al: Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 45:1446–1451. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Toy W, Shen Y, Won H, Green B, Sakr RA, Will M, Li Z, Gala K, Fanning S, King TA, et al: ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 45:1439–1445. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Bartels S, Christgen M, Luft A, Persing S, Jödecke K, Lehmann U and Kreipe H: Estrogen receptor (ESR1) mutation in bone metastases from breast cancer. Mod Pathol. 31:56–61. 2018. View Article : Google Scholar : PubMed/NCBI

12 

Yanagawa T, Kagara N, Miyake T, Tanei T, Naoi Y, Shimoda M, Shimazu K, Kim SJ and Noguchi S: Detection of ESR1 mutations in plasma and tumors from metastatic breast cancer patients using next-generation sequencing. Breast Cancer Res Treat. 163:231–240. 2017. View Article : Google Scholar : PubMed/NCBI

13 

Lefebvre C, Bachelot T, Filleron T, Pedrero M, Campone M, Soria JC, Massard C, Lévy C, Arnedos M, Lacroix-Triki M, et al: Mutational profile of metastatic breast cancers: A retrospective analysis. PLoS Med. 13:e10022012016. View Article : Google Scholar : PubMed/NCBI

14 

Clarke R, Tyson JJ and Dixon JM: Endocrine resistance in breast cancer-An overview and update. Mol Cell Endocrinol. 418:220–234. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Backes FJ, Walker CJ, Goodfellow PJ, Hade EM, Agarwal G, Mutch D, Cohn DE and Suarez AA: Estrogen receptor-alpha as a predictive biomarker in endometrioid endometrial cancer. Gynecol Oncol. 141:312–317. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Cancer Genome Atlas Network, ; Muzny DM, Bainbridge MN, Chang K, Dinh HH, Drummond JA, Fowler G, Kovar CL, Lewis LR, Morgan MB, et al: Comprehensive molecular characterization of human colon and rectal cancer. Nature. 487:330–337. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Ojesina AI, Lichtenstein L, Freeman SS, Pedamallu CS, Imaz-Rosshandler I, Pugh TJ, Cherniack AD, Ambrogio L, Cibulskis K, Bertelsen B, et al: Landscape of genomic alterations in cervical carcinomas. Nature. 506:371–375. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Muller E, Brault B, Holmes A, Legros A, Jeannot E, Campitelli M, Rousselin A, Goardon N, Frébourg T, Krieger S, et al: Genetic profiles of cervical tumors by high-throughput sequencing for personalized medical care. Cancer Med. 4:1484–1493. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Sjöblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, et al: The consensus coding sequences of human breast and colorectal cancers. Science. 314:268–274. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Banerji S, Cibulskis K, Rangel-Escareno C, Brown KK, Carter SL, Frederick AM, Lawrence MS, Sivachenko AY, Sougnez C, Zou L, et al: Sequence analysis of mutations and translocations across breast cancer subtypes. Nature. 486:405–409. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Cancer Genome Atlas Research Network; Albert Einstein College of Medicine; Analytical Biological Services; Barretos Cancer Hospital; Baylor College of Medicine; Beckman Research Institute of City of Hope; Buck Institute for Research on Aging; Canada's Michael Smith Genome Sciences Centre; Harvard Medical School; Helen F. Graham Cancer Center & Research Institute at Christiana Care Health Services, ; et al Integrated genomic and molecular characterization of cervical cancer. Nature. 543:378–384. 2017. View Article : Google Scholar : PubMed/NCBI

22 

den Boon JA, Pyeon D, Wang SS, Horswill M, Schiffman M, Sherman M, Zuna RE, Wang Z, Hewitt SM, Pearson R, et al: Molecular transitions from papillomavirus infection to cervical precancer and cancer: Role of stromal estrogen receptor signaling. Proc Natl Acad Sci USA. 112:E3255–E3264. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Bronowicka-Kłys DE, Lianeri M and Jagodziński PP: The role and impact of estrogens and xenoestrogen on the development of cervical cancer. Biomed Pharmacother. 84:1945–1953. 2016. View Article : Google Scholar : PubMed/NCBI

24 

Leung YK, Lee MT, Lam HM, Tarapore P and Ho SM: Estrogen receptor-beta and breast cancer: Translating biology into clinical practice. Steroids. 77:727–737. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Vazquez Rodriguez G, Abrahamsson A, Jensen LD and Dabrosin C: Estradiol promotes breast cancer cell migration via recruitment and activation of neutrophils. Cancer Immunol Res. 5:234–247. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Zou Y, Liu FY, Wu J, Wan L, Fang SF, Zhang ZY, Luo Y, Chen MH, Huang MZ, He M and Huang OP: Mutational analysis of the RAS/RAF/MEK/ERK signaling pathway in 260 Han Chinese patients with cervical carcinoma. Oncol Lett. 14:2427–2431. 2017. View Article : Google Scholar : PubMed/NCBI

27 

Schwarz JM, Cooper DN, Schuelke M and Seelow D: MutationTaster2: Mutation prediction for the deep-sequencing age. Nat Methods. 11:361–362. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS and Sunyaev SR: A method and server for predicting damaging missense mutations. Nat Methods. 7:248–249. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Tamura K, Dudley J, Nei M and Kumar S: MEGA4: Molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol. 24:1596–1599. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Johansson MU, Zoete V, Michielin O and Guex N: Defining and searching for structural motifs using DeepView/Swiss-PdbViewer. BMC Bioinformatics. 13:1732012. View Article : Google Scholar : PubMed/NCBI

31 

Koide A, Abbatiello S, Rothgery L and Koide S: Probing protein conformational changes in living cells by using designer binding proteins: Application to the estrogen receptor. Proc Natl Acad Sci USA. 99:1253–1258. 2002. View Article : Google Scholar : PubMed/NCBI

32 

1000 Genomes Project Consortium, ; Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, Kang HM, Marth GT and McVean GA: An integrated map of genetic variation from 1,092 human genomes. Nature. 491:56–65. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O'Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB, et al: Analysis of protein-coding genetic variation in 60,706 humans. Nature. 536:285–291. 2016. View Article : Google Scholar : PubMed/NCBI

34 

Fuqua SA, Wiltschke C, Zhang QX, Borg A, Castles CG, Friedrichs WE, Hopp T, Hilsenbeck S, Mohsin S, O'Connell P and Allred DC: A hypersensitive estrogen receptor-alpha mutation in premalignant breast lesions. Cancer Res. 60:4026–4029. 2000.PubMed/NCBI

35 

Conway K, Parrish E, Edmiston SN, Tolbert D, Tse CK, Geradts J, Livasy CA, Singh H, Newman B and Millikan RC: The estrogen receptor-alpha A908G (K303R) mutation occurs at a low frequency in invasive breast tumors: Results from a population-based study. Breast Cancer Res. 7:R871–R880. 2005. View Article : Google Scholar : PubMed/NCBI

36 

Herynk MH, Parra I, Cui Y, Beyer A, Wu MF, Hilsenbeck SG and Fuqua SA: Association between the estrogen receptor alpha A908G mutation and outcomes in invasive breast cancer. Clin Cancer Res. 13:3235–3243. 2007. View Article : Google Scholar : PubMed/NCBI

37 

Abbasi S, Rasouli M, Nouri M and Kalbasi S: Association of estrogen receptor-α A908G (K303R) mutation with breast cancer risk. Int J Clin Exp Med. 6:39–49. 2013.PubMed/NCBI

38 

Lim B, Mun J, Kim JH, Kim CW, Roh SA, Cho DH, Kim YS, Kim SY and Kim JC: Genome-wide mutation profiles of colorectal tumors and associated liver metastases at the exome and transcriptome levels. Oncotarget. 6:22179–22190. 2015. View Article : Google Scholar : PubMed/NCBI

39 

Wang P, Bahreini A, Gyanchandani R, Lucas PC, Hartmaier RJ, Watters RJ, Jonnalagadda AR, Trejo Bittar HE, Berg A, Hamilton RL, et al: Sensitive detection of mono- and polyclonal ESR1 mutations in primary tumors, metastatic lesions, and cell-free DNA of breast cancer patients. Clin Cancer Res. 22:1130–1137. 2016. View Article : Google Scholar : PubMed/NCBI

40 

Niu J, Andres G, Kramer K, Kundranda MN, Alvarez RH, Klimant E, Parikh AR, Tan B, Staren ED and Markman M: Incidence and clinical significance of ESR1 mutations in heavily pretreated metastatic breast cancer patients. Onco Targets Ther. 8:3323–3328. 2015. View Article : Google Scholar : PubMed/NCBI

41 

Takeshita T, Yamamoto Y, Yamamoto-Ibusuki M, Inao T, Sueta A, Fujiwara S, Omoto Y and Iwase H: Droplet digital polymerase chain reaction assay for screening of ESR1 mutations in 325 breast cancer specimens. Transl Res. 166:540–553.e2. 2015. View Article : Google Scholar : PubMed/NCBI

42 

Cui Y, Zhang M, Pestell R, Curran EM, Welshons WV and Fuqua SA: Phosphorylation of estrogen receptor alpha blocks its acetylation and regulates estrogen sensitivity. Cancer Res. 64:9199–9208. 2004. View Article : Google Scholar : PubMed/NCBI

43 

Toy W, Weir H, Razavi P, Lawson M, Goeppert AU, Mazzola AM, Smith A, Wilson J, Morrow C, Wong WL, et al: Activating ESR1 mutations differentially affect the efficacy of ER antagonists. Cancer Discov. 7:277–287. 2017. View Article : Google Scholar : PubMed/NCBI

44 

Segovia-Mendoza M, Jurado R, Mir R, Medina LA, Prado-Garcia H and Garcia-Lopez P: Antihormonal agents as a strategy to improve the effect of chemo-radiation in cervical cancer: In vitro and in vivo study. BMC Cancer. 15:212015. View Article : Google Scholar : PubMed/NCBI

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September-2019
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Spandidos Publications style
Yang XM, Wu ZM, Huang H, Chu XY, Lou J, Xu LX, Chen YT, Wang LQ and Huang OP: Estrogen receptor 1 mutations in 260 cervical cancer samples from Chinese patients. Oncol Lett 18: 2771-2776, 2019
APA
Yang, X., Wu, Z., Huang, H., Chu, X., Lou, J., Xu, L. ... Huang, O. (2019). Estrogen receptor 1 mutations in 260 cervical cancer samples from Chinese patients. Oncology Letters, 18, 2771-2776. https://doi.org/10.3892/ol.2019.10612
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Yang, X., Wu, Z., Huang, H., Chu, X., Lou, J., Xu, L., Chen, Y., Wang, L., Huang, O."Estrogen receptor 1 mutations in 260 cervical cancer samples from Chinese patients". Oncology Letters 18.3 (2019): 2771-2776.
Chicago
Yang, X., Wu, Z., Huang, H., Chu, X., Lou, J., Xu, L., Chen, Y., Wang, L., Huang, O."Estrogen receptor 1 mutations in 260 cervical cancer samples from Chinese patients". Oncology Letters 18, no. 3 (2019): 2771-2776. https://doi.org/10.3892/ol.2019.10612