Novel TRERF1 mutations in Chinese patients with ovarian endometriosis

Cao,Bianna; Zeng,Yuanfeng; Wu,Fei; Liu,Jun; Shuang,Zeliang; Xu,Xiaoyun; Guo,Jiubai

doi:10.3892/mmr.2018.8510

Novel TRERF1 mutations in Chinese patients with ovarian endometriosis

Authors:
- Bianna Cao
- Yuanfeng Zeng
- Fei Wu
- Jun Liu
- Zeliang Shuang
- Xiaoyun Xu
- Jiubai Guo
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Affiliations: Department of Gynecology, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China, Department of Pathology, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi 330006, P.R. China
Published online on: January 26, 2018 https://doi.org/10.3892/mmr.2018.8510
Pages: 5435-5439

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Abstract

Endometriosis is an estrogen-dependent precancerous lesion exhibiting frequently perturbed level of steroid hormones and transcriptional‑regulating factor 1 (TRERF1) has a crucial role in the production of steroid hormones including estrogen. Endometriosis has previously been revealed to be a precancerous lesion that harbors somatic mutations in cancer‑associated genes. Therefore, the authors of the present study hypothesize that TRERF1 aberrations may be involved in the development of endometriosis. In the present study, endometriotic lesions and paired blood samples from 92 individuals with ovarian endometriosis were analyzed for the potential presence of TRERF1 mutations by sequencing the entire coding region and the corresponding intron‑exon boundaries of the TRERF1 gene. Two heterozygous missense somatic mutations [c.3166A>C (p.K1056Q) and c.3187 G>A (p.G1063R)] in the TRERF1 gene were identified in two out of 92 ectopic endometria (2.2%), to the best of our knowledge, these mutations have not been previously reported. From the two samples with TRERF1 mutations, one sample was from a 42‑year‑old patient also diagnosed with uterine leiomyoma and the other mutation was identified in a 36‑year‑old woman exhibiting no other apparent gynecological conditions. The evolutionary conservation analysis and in silico prediction of these TRERF1 mutations suggested that they may be pathogenic. To the best of our knowledge, the present study was the first to identify 2 novel, potentially ‘disease‑causing’ TRERF1 somatic mutations in the endometriotic lesions in 2 out of 92 patients with ovarian endometriosis; therefore, TRERF1 mutations may be involved in the pathogenesis of ovarian endometriosis.

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1	Arosh JA, Lee J, Balasubbramanian D, Stanley JA, Long CR, Meagher MW, Osteen KG, Bruner-Tran KL, Burghardt RC, Starzinski-Powitz A and Banu SK: Molecular and preclinical basis to inhibit PGE2 receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis. Proc Natl Acad Sci USA. 112:pp. 9716–9721. 2015; View Article : Google Scholar : PubMed/NCBI
2	Samartzis EP, Noske A, Dedes KJ, Fink D and Imesch P: ARID1A mutations and PI3K/AKT pathway alterations in endometriosis and endometriosis-associated ovarian carcinomas. Int J Mol Sci. 14:18824–18849. 2013. View Article : Google Scholar : PubMed/NCBI
3	Leone Roberti Maggiore U, Ferrero S, Mangili G, Bergamini A, Inversetti A, Giorgione V, Viganò P and Candiani M: A systematic review on endometriosis during pregnancy: Diagnosis, misdiagnosis, complications and outcomes. Hum Reprod Update. 22:70–103. 2016. View Article : Google Scholar : PubMed/NCBI
4	Vigano P, Corti L and Berlanda N: Beyond infertility: Obstetrical and postpartum complications associated with endometriosis and adenomyosis. Fertil Steril. 104:802–812. 2015. View Article : Google Scholar : PubMed/NCBI
5	Fadhlaoui A, Bouquet de la Jolinière J and Feki A: Endometriosis and infertility: How and when to treat? Front Surg. 1:242014. View Article : Google Scholar : PubMed/NCBI
6	Tosti C, Pinzauti S, Santulli P, Chapron C and Petraglia F: Pathogenetic mechanisms of deep infiltrating endometriosis. Reprod Sci. 22:1053–1059. 2015. View Article : Google Scholar : PubMed/NCBI
7	Richards EG, Zheng Y, Shenoy CC, Ainsworth AJ, Delaney AA, Jones TL, Khan Z and Daftary GS: KLF11 is an epigenetic mediator of DRD2/dopaminergic signaling in endometriosis. Reprod Sci. 24:1129–1138. 2017. View Article : Google Scholar : PubMed/NCBI
8	Uimari O, Rahmioglu N, Nyholt DR, Vincent K, Missmer SA, Becker C, Morris AP, Montgomery GW and Zondervan KT: Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis. Hum Reprod. 32:780–793. 2017. View Article : Google Scholar : PubMed/NCBI
9	Yotova I, Hsu E, Do C, Gaba A, Sczabolcs M, Dekan S, Kenner L, Wenzl R and Tycko B: Epigenetic alterations affecting transcription factors and signaling pathways in stromal cells of endometriosis. PLoS One. 12:e01708592017. View Article : Google Scholar : PubMed/NCBI
10	Matsumoto T, Yamazaki M, Takahashi H, Kajita S, Suzuki E, Tsuruta T and Saegusa M: Distinct β-catenin and PIK3CA mutation profiles in endometriosis-associated ovarian endometrioid and clear cell carcinomas. Am J Clin Pathol. 144:452–463. 2015. View Article : Google Scholar : PubMed/NCBI
11	Pavlidou A and Vlahos NF: Endometriosis and ovarian cancer: Clinical and molecular aspects. Minerva Endocrinol. 39:155–165. 2014.PubMed/NCBI
12	Burghaus S, Fasching PA, Häberle L, Rübner M, Büchner K, Blum S, Engel A, Ekici AB, Hartmann A, Hein A, et al: Genetic risk factors for ovarian cancer and their role for endometriosis risk. Gynecol Oncol. 145:142–147. 2017. View Article : Google Scholar : PubMed/NCBI
13	Vestergaard AL, Thorup K, Knudsen UB, Munk T, Rosbach H, Poulsen JB, Guldberg P and Martensen PM: Oncogenic events associated with endometrial and ovarian cancers are rare in endometriosis. Mol Hum Reprod. 17:758–761. 2011. View Article : Google Scholar : PubMed/NCBI
14	Li X, Zhang Y, Zhao L, Wang L, Wu Z, Mei Q, Nie J, Li X, Li Y, Fu X, et al: Whole-exome sequencing of endometriosis identifies frequent alterations in genes involved in cell adhesion and chromatin-remodeling complexes. Hum Mol Genet. 23:6008–6021. 2014. View Article : Google Scholar : PubMed/NCBI
15	Anglesio MS, Papadopoulos N, Ayhan A, Nazeran TM, Noë M, Horlings HM, Lum A, Jones S, Senz J, Seckin T, et al: Cancer-associated mutations in endometriosis without cancer. N Engl J Med. 376:1835–1848. 2017. View Article : Google Scholar : PubMed/NCBI
16	Gizard F, El-Alfy M, Duguay Y, Lavallée B, DeWitte F, Staels B, Beatty BG and Hum DW: Function of the transcriptional regulating protein of 132 kDa (TReP-132) on human P450scc gene expression. Endocr Res. 28:559–574. 2002. View Article : Google Scholar : PubMed/NCBI
17	Gizard F, Teissier E, Dufort I, Luc G, Luu-The V, Staels B and Hum DW: The transcriptional regulating protein of 132 kDa (TReP-132) differentially influences steroidogenic pathways in human adrenal NCI-H295 cells. J Mol Endocrinol. 32:557–569. 2004. View Article : Google Scholar : PubMed/NCBI
18	Reis FM, Petraglia F and Taylor RN: Endometriosis: Hormone regulation and clinical consequences of chemotaxis and apoptosis. Hum Reprod Update. 19:406–418. 2013. View Article : Google Scholar : PubMed/NCBI
19	Vercellini P, Viganò P, Somigliana E and Fedele L: Endometriosis: Pathogenesis and treatment. Nat Rev Endocrinol. 10:261–275. 2014. View Article : Google Scholar : PubMed/NCBI
20	Gizard F, Lavallee B, DeWitte F, Teissier E, Staels B and Hum DW: The transcriptional regulating protein of 132 kDa (TReP-132) enhances P450scc gene transcription through interaction with steroidogenic factor-1 in human adrenal cells. J Biol Chem. 277:39144–39155. 2002. View Article : Google Scholar : PubMed/NCBI
21	Wu J, Zou Y, Luo Y, Guo JB, Liu FY, Zhou JY, Zhang ZY, Wan L and Huang OP: Prevalence and clinical significance of mediator complex subunit 12 mutations in 362 Han Chinese samples with uterine leiomyoma. Oncol Lett. 14:47–54. 2017. View Article : Google Scholar : PubMed/NCBI
22	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
23	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
24	Adzhubei I, Jordan DM and Sunyaev SR: Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet. Jan;2013.doi: 10.1002/0471142905.hg0720s76. View Article : Google Scholar : PubMed/NCBI
25	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
26	Stenson PD, Mort M, Ball EV, Evans K, Hayden M, Heywood S, Hussain M, Phillips AD and Cooper DN: The human gene mutation database: Towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies. Hum Genet. 136:665–677. 2017. View Article : Google Scholar : PubMed/NCBI