New Candidate Predisposition Genes for Hereditary Breast Cancer: SLIT3, CREB3, USP39
DOI:
https://doi.org/10.31964/mltj.v7i1.401Keywords:
Hereditary breast and ovarian cancer, next generation sequencing, genetic oncology, breast cancer genetics, single-nucleotide polymorphismAbstract
Breast cancer is the most common type of malignant neoplasm in women. BRCA1 and BRCA2 are the most commonly mutated genes, but only up to 30% of hereditary breast cancer cases are attributed to alterations in these genes. A large proportion of genetic causes of hereditary breast cancer remains unknown. Thus, the search for new hereditary mutations and establishing a genetic alteration in each case of hereditary breast cancer is a clinically significant task; be the goal of our research. Next-generation sequencing (NGS) allows for simultaneous analysis of hundreds to thousands of genes at one time. We analyzed the genetic material of 49 patients of the northwest Russian population with clinical signs of hereditary breast cancer and identified new mutations associated with hereditary breast cancer. Research results show two missense mutations - SLIT3 p.Arg154Cys, CREB3 p.Lys157Glu, and truncating mutation - USP39 c.*208G>C. Research conclusion; The identified mutations can explain only a tiny fraction of hereditary breast cancer cases (0.7% to 1.1%). The next step to increase the practical value of the detected alterations should be the analysis of biological characteristics of tumors in carriers of these mutations that can potentially become a target for chemotherapy.References
Afghahi A., Kurian W. (2017). A the changing landscape of genetic testing for inherited breast cancer predisposition. Current treatment options in oncology, 18(27), 10.1007/s11864-017-0468-y
Apostolou P., Fostira F. (2013). Hereditary breast cancer: the era of new susceptibility genes. BioMed Research International, -P, 1-11. 10.1155/2013/747318
Balmana J., Digiovanni L, Gaddam P, et al. (2016). Conflicting interpretation of genetic variants and Cancer risk by commercial laboratories as assessed by the prospective registry of multiplex testing. Journal of Clinical Oncology, 34, 4071-4078. 10.1200/JCO.2016.68.4316
Couch FJ, Shimelis H, Hu C, et al. (2017). Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncology, 3, 1190-1196. 10.1001/jamaoncol.2017.0424
Federici, G., Soddu, S. (2020). Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers. Journal of Experimental & Clinical Cancer Research, 39, 10.1186/s13046-020-01554-6
Goldgar DE, Easton DF, Deffenbaugh AM, et al. (2004). Integrated evaluation of DNA sequence variants of unknown clinical significance: application to BRCA1 and BRCA2. The American Journal of Human Genetics, 75, 535-544. 10.1086/424388
Graffeo R., Livraghi L. (2016). Time to incorporate germline multigene panel testing into breast and ovarian cancer patient care. Breast Cancer Res treat, 160, 393-410. 10.1007/s10549-016-4003-9
Hauke J., Horvath J., Groß E. (2018). Gene panel testing of 5589 BRCA1/2-negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and ovarian Cancer. Cancer Med, 7, 1349-1358. 10.1002/cam4.1376
Howley BV, Link LA, Grelet S, et al. (2018). A CREB3-regulated ER-Golgi trafficking signature promotes metastatic progression in breast cancer. Oncogene, 37, 1308-1325. 10.1038/s41388-017-0023-0
Joseph L, Cankovic M, Caughron S, et al. (2016). The Spectrum of clinical Utilities in Molecular Pathology Testing Procedures for inherited conditions and Cancer: a report of the Association for Molecular Pathology. The Journal of Molecular Diagnostics, 18, 605-619. 10.1016/j.jmoldx.2016.05.007
Kast K., Rhiem K., Wappenschmidt B. (2016). Prevalence of BRCA1/2 germline mutations in 21 401 families with breast and ovarian cancer. J. Med. Genet, 53, 465-471. 10.1136/jmedgenet-2015-103672
Kim Y, Kim J, Jang SW, Ko J. (2015). The role of sLZIP in cyclin D3-mediated negative regulation of androgen receptor transactivation and its involvement in prostate cancer. Oncogene, 34, 226-236. 10.1038/onc.2013.538
Lu H.M., Li s., Black M.H., Lee s. et al. (2018). Association of Breast and ovarian Cancers With Predisposition Genes Identified by Large-scale sequencing. JAMA oncol, 10.1001/jamaoncol.2018.2956
Marlow R, Strickland P, Lee JS, et al. (2008). SLITs suppress tumor growth in vivo by silencing Sdf1/Cxcr4 within breast epithelium. Cancer Research, 68, 7819-7827. 10.1158/0008-5472.CAN-08-1357
Nelson H.D., Pappas M., Zakher B. (2014). Risk assessment, genetic counseling, and genetic testing for BRCA- related cancer in women: a systematic review to update the U.S. Preventive services task Force recommendation. Ann Intern. Med, 160, 255-266. 10.7326/M13-1684
Ng L, Chow AKM, Man JHW, et al. (2018). Suppression of Slit3 induces tumor proliferation and chemoresistance in hepatocellular carcinoma through activation of GSK3β/β-catenin pathway. BMC Cancer, 18, 1. 10.1186/s12885-018-4326-5
Oldfield CJ, Dunker AK. (2014). Intrinsically disordered proteins and intrinsically disordered protein regions. Annu Rev Biochem, 83, 553-584. 10.2174/092986610791498984
Park E, Kang H, Kim J, Ko J. (2014). The role of sLZIP in transcriptional regulation of c-Jun and involvement in migration and invasion of cervical cancer cells. Cell Physiol Biochem, 33, 151-164. 10.1159/000356658
Plon, S. E., Eccles, D. M., Easton, D. (2008). Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results. Human Mutation, 29, 1282-1291. 10.1002/humu.20880
Talhouet S, Peron J, Vuilleumier A, et al. (2020). Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes. Scientific Reports, 10.1038/s41598-020-63759-1
Tsaousis, G.N., Papadopoulou, E., Apessos, A. et al. (2019). Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations. BMC Cancer, 19, 535. https://doi.org/10.1186/s12885-019-5756-4
Wang H, Ji X, Liu X, et al. (2013). Lentivirus-mediated inhibition of USP39 suppresses the growth of breast cancer cells in vitro. Oncology Reports, 30, 2871-2877. 10.3892/or.2013.2798
Wang YA, Jian JW, Hung CF, et al. (2018). Germline breast cancer susceptibility gene mutations and breast cancer outcomes. BMC Cancer, 18, 10.1186/s12885-018-4229-5
Wu J, Chen Y, Geng G, Li L, Yin P, Nowsheen S, Li Y: Wu C, Liu J, Zhao F, Kim W, Zhou Q, Huang J, Guo G, Zhang C, Tu X, Gao X, Lou Z, Luo K, Qiao H, Yuan J. (2019). USP39 regulates DNA damage response and chemo-radiation resistance by deubiquitinating and stabilizing CHK2. Cancer Lett, 1, 114-124. 10.1016/j.canlet.2019.02.015.
Wu Y, Xie Z, Chen J. (2019). Circular RNA circTADA2A promotes osteosarcoma progression and metastasis by sponging miR-203a-3p and regulating CREB3 expression. Mol Cancer, 2, 73. 10.1186/s12943-019-1007-1. PMID: 30940151 PMCID: PMC6444890
Xing Z, Sun F, He W, et al. (2018). Downregulation of ubiquitin-specific peptidase 39 suppresses the proliferation and induces the apoptosis of human colorectal cancer cells. Oncology Letters, 15, 5443-5450. 10.3892/ol.2018.8061
Xu Y, Zhu MR, Zhang JY, et al. (2018). Knockdown of ubiquitin specific peptidase 39 inhibits the malignant progression of human renal cell carcinoma. Molecular Medicine Reports, 17, 4729-4735. 10.3892/mmr.2018.8421
Yuan X, Sun X, Shi X, et al. (2015). USP39 promotes the growth of human hepatocellular carcinoma in vitro and in vivo. Oncology Reports, 34, 823-832. 10.3892/or.2015.4065
Zhang C, Guo H, Li B, et al. (2015). Effects of Slit3 silencing on the invasive ability of lung carcinoma A549 cells. Oncology Reports, 34, 952-960. 10.3892/or.2015.4031
Zhao F, Wang N, Yi Y, et al. (2016). Knockdown of CREB3/Luman by shRNA in Mouse Granulosa Cells Results in Decreased Estradiol and Progesterone Synthesis and Promotes Cell Proliferation. PLoS ONE, 11, 10.1371/journal.pone.0168246.
Apostolou P., Fostira F. (2013). Hereditary breast cancer: the era of new susceptibility genes. BioMed Research International, -P, 1-11. 10.1155/2013/747318
Balmana J., Digiovanni L, Gaddam P, et al. (2016). Conflicting interpretation of genetic variants and Cancer risk by commercial laboratories as assessed by the prospective registry of multiplex testing. Journal of Clinical Oncology, 34, 4071-4078. 10.1200/JCO.2016.68.4316
Couch FJ, Shimelis H, Hu C, et al. (2017). Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncology, 3, 1190-1196. 10.1001/jamaoncol.2017.0424
Federici, G., Soddu, S. (2020). Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers. Journal of Experimental & Clinical Cancer Research, 39, 10.1186/s13046-020-01554-6
Goldgar DE, Easton DF, Deffenbaugh AM, et al. (2004). Integrated evaluation of DNA sequence variants of unknown clinical significance: application to BRCA1 and BRCA2. The American Journal of Human Genetics, 75, 535-544. 10.1086/424388
Graffeo R., Livraghi L. (2016). Time to incorporate germline multigene panel testing into breast and ovarian cancer patient care. Breast Cancer Res treat, 160, 393-410. 10.1007/s10549-016-4003-9
Hauke J., Horvath J., Groß E. (2018). Gene panel testing of 5589 BRCA1/2-negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and ovarian Cancer. Cancer Med, 7, 1349-1358. 10.1002/cam4.1376
Howley BV, Link LA, Grelet S, et al. (2018). A CREB3-regulated ER-Golgi trafficking signature promotes metastatic progression in breast cancer. Oncogene, 37, 1308-1325. 10.1038/s41388-017-0023-0
Joseph L, Cankovic M, Caughron S, et al. (2016). The Spectrum of clinical Utilities in Molecular Pathology Testing Procedures for inherited conditions and Cancer: a report of the Association for Molecular Pathology. The Journal of Molecular Diagnostics, 18, 605-619. 10.1016/j.jmoldx.2016.05.007
Kast K., Rhiem K., Wappenschmidt B. (2016). Prevalence of BRCA1/2 germline mutations in 21 401 families with breast and ovarian cancer. J. Med. Genet, 53, 465-471. 10.1136/jmedgenet-2015-103672
Kim Y, Kim J, Jang SW, Ko J. (2015). The role of sLZIP in cyclin D3-mediated negative regulation of androgen receptor transactivation and its involvement in prostate cancer. Oncogene, 34, 226-236. 10.1038/onc.2013.538
Lu H.M., Li s., Black M.H., Lee s. et al. (2018). Association of Breast and ovarian Cancers With Predisposition Genes Identified by Large-scale sequencing. JAMA oncol, 10.1001/jamaoncol.2018.2956
Marlow R, Strickland P, Lee JS, et al. (2008). SLITs suppress tumor growth in vivo by silencing Sdf1/Cxcr4 within breast epithelium. Cancer Research, 68, 7819-7827. 10.1158/0008-5472.CAN-08-1357
Nelson H.D., Pappas M., Zakher B. (2014). Risk assessment, genetic counseling, and genetic testing for BRCA- related cancer in women: a systematic review to update the U.S. Preventive services task Force recommendation. Ann Intern. Med, 160, 255-266. 10.7326/M13-1684
Ng L, Chow AKM, Man JHW, et al. (2018). Suppression of Slit3 induces tumor proliferation and chemoresistance in hepatocellular carcinoma through activation of GSK3β/β-catenin pathway. BMC Cancer, 18, 1. 10.1186/s12885-018-4326-5
Oldfield CJ, Dunker AK. (2014). Intrinsically disordered proteins and intrinsically disordered protein regions. Annu Rev Biochem, 83, 553-584. 10.2174/092986610791498984
Park E, Kang H, Kim J, Ko J. (2014). The role of sLZIP in transcriptional regulation of c-Jun and involvement in migration and invasion of cervical cancer cells. Cell Physiol Biochem, 33, 151-164. 10.1159/000356658
Plon, S. E., Eccles, D. M., Easton, D. (2008). Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results. Human Mutation, 29, 1282-1291. 10.1002/humu.20880
Talhouet S, Peron J, Vuilleumier A, et al. (2020). Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes. Scientific Reports, 10.1038/s41598-020-63759-1
Tsaousis, G.N., Papadopoulou, E., Apessos, A. et al. (2019). Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations. BMC Cancer, 19, 535. https://doi.org/10.1186/s12885-019-5756-4
Wang H, Ji X, Liu X, et al. (2013). Lentivirus-mediated inhibition of USP39 suppresses the growth of breast cancer cells in vitro. Oncology Reports, 30, 2871-2877. 10.3892/or.2013.2798
Wang YA, Jian JW, Hung CF, et al. (2018). Germline breast cancer susceptibility gene mutations and breast cancer outcomes. BMC Cancer, 18, 10.1186/s12885-018-4229-5
Wu J, Chen Y, Geng G, Li L, Yin P, Nowsheen S, Li Y: Wu C, Liu J, Zhao F, Kim W, Zhou Q, Huang J, Guo G, Zhang C, Tu X, Gao X, Lou Z, Luo K, Qiao H, Yuan J. (2019). USP39 regulates DNA damage response and chemo-radiation resistance by deubiquitinating and stabilizing CHK2. Cancer Lett, 1, 114-124. 10.1016/j.canlet.2019.02.015.
Wu Y, Xie Z, Chen J. (2019). Circular RNA circTADA2A promotes osteosarcoma progression and metastasis by sponging miR-203a-3p and regulating CREB3 expression. Mol Cancer, 2, 73. 10.1186/s12943-019-1007-1. PMID: 30940151 PMCID: PMC6444890
Xing Z, Sun F, He W, et al. (2018). Downregulation of ubiquitin-specific peptidase 39 suppresses the proliferation and induces the apoptosis of human colorectal cancer cells. Oncology Letters, 15, 5443-5450. 10.3892/ol.2018.8061
Xu Y, Zhu MR, Zhang JY, et al. (2018). Knockdown of ubiquitin specific peptidase 39 inhibits the malignant progression of human renal cell carcinoma. Molecular Medicine Reports, 17, 4729-4735. 10.3892/mmr.2018.8421
Yuan X, Sun X, Shi X, et al. (2015). USP39 promotes the growth of human hepatocellular carcinoma in vitro and in vivo. Oncology Reports, 34, 823-832. 10.3892/or.2015.4065
Zhang C, Guo H, Li B, et al. (2015). Effects of Slit3 silencing on the invasive ability of lung carcinoma A549 cells. Oncology Reports, 34, 952-960. 10.3892/or.2015.4031
Zhao F, Wang N, Yi Y, et al. (2016). Knockdown of CREB3/Luman by shRNA in Mouse Granulosa Cells Results in Decreased Estradiol and Progesterone Synthesis and Promotes Cell Proliferation. PLoS ONE, 11, 10.1371/journal.pone.0168246.
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Published
2021-10-26
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Zagorodnev, K., Romanko, A., Sokolenko, A. P., Bizin, I., & Kuligina, E. S. (2021). New Candidate Predisposition Genes for Hereditary Breast Cancer: SLIT3, CREB3, USP39. Medical Laboratory Technology Journal, 7(1), 92–100. https://doi.org/10.31964/mltj.v7i1.401
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